{ "category": "Cancer Predisposition", "panel_settings": { "default_inheritance_mode": "autosomal_dominant_or_context_dependent", "default_noncoding_exact_clinvar_policy": "manual_review", "preferred_transcript_policy": "ensembl_canonical_then_primary_protein_coding", "reporting_assembly": "GRCh38", "species": "homo_sapiens" }, "report_snippets": { "report_title_suffix": "review", "important_text": "This report is conservative for broad CNV segments, but exact ClinVar pathogenic non-coding matches are retained as manual-review candidates rather than being automatically discarded.", "negative_gene_assessment": "No clinically significant finding identified", "negative_small_variant_assessment": "No clinically significant small variant identified", "negative_structural_assessment": "No reportable structural event identified", "negative_review_assessment": "No non-coding exact ClinVar review candidates identified", "positive_status": "Clinically significant finding identified", "carrier_status": "Actionable carrier finding identified", "review_status": "Manual review required", "structural_status": "Structural review recommended", "negative_status": "Clinically significant finding not identified" }, "classification_display": { "pathogenic": { "headline": "Clinically Significant Mutation Identified", "badge": "Positive", "severity": "high", "table_label": "High Risk", "patient_summary": "This finding is associated with increased inherited disease risk." }, "likely_pathogenic": { "headline": "Likely Clinically Significant Mutation Identified", "badge": "Positive", "severity": "high", "table_label": "Increased Risk", "patient_summary": "This finding is likely to be associated with increased inherited disease risk." }, "vus": { "headline": "Variant of Uncertain Significance Identified", "badge": "VUS", "severity": "moderate", "table_label": "Uncertain", "patient_summary": "There is currently not enough evidence to determine whether this finding is clinically significant." }, "carrier": { "headline": "Actionable Carrier Finding Identified", "badge": "Carrier", "severity": "moderate", "table_label": "Carrier", "patient_summary": "This finding may be relevant for reproductive risk and family planning." }, "review": { "headline": "Manual Review Required", "badge": "Review", "severity": "moderate", "table_label": "Review Needed", "patient_summary": "A potentially relevant finding was identified but requires specialist review before final interpretation." }, "structural_review": { "headline": "Structural Review Recommended", "badge": "Review", "severity": "moderate", "table_label": "Structural Review", "patient_summary": "A potentially relevant structural finding was identified and should be reviewed before final interpretation." }, "negative": { "headline": "No Clinically Significant Finding Identified", "badge": "Negative", "severity": "low", "table_label": "No Significant Finding", "patient_summary": "No clinically significant finding was identified in the genes analysed for this category." } }, "report_sections": { "clinical_history": { "title": "Clinical History Analysis", "default_text": "Other clinical factors may influence individualised management. This analysis may be incomplete if details about diagnoses, ages, family relationships, or other factors were omitted or unclear." }, "additional_findings": { "title_no_vus": "No variant(s) of uncertain significance identified", "title_with_vus": "Additional Findings", "default_text": "Likely benign and benign variants are not reported. Variants of uncertain significance are reported when identified." }, "classification_programme": { "title": "Variant Classification", "default_text": "Variant classifications may change over time as new evidence becomes available." }, "technical_appendix": { "title": "Technical Appendix", "default_text": "Technical details are provided for transparency and should be interpreted in the context of the final clinical classification." } }, "consequence_phrases": { "frameshift_variant": { "clinical_label": "Deleterious", "patient_phrase": "This change disrupts the reading frame and is expected to alter normal protein function." }, "stop_gained": { "clinical_label": "Deleterious", "patient_phrase": "This change introduces an early stop signal and is expected to shorten the protein." }, "splice_acceptor_variant": { "clinical_label": "Likely disruptive", "patient_phrase": "This change may interfere with normal RNA splicing and alter the resulting protein." }, "splice_donor_variant": { "clinical_label": "Likely disruptive", "patient_phrase": "This change may interfere with normal RNA splicing and alter the resulting protein." }, "missense_variant": { "clinical_label": "Protein-altering", "patient_phrase": "This change alters one amino acid in the protein and requires classification in context." }, "start_lost": { "clinical_label": "Likely disruptive", "patient_phrase": "This change may disrupt the normal start of protein translation." }, "stop_lost": { "clinical_label": "Protein-altering", "patient_phrase": "This change may extend the protein beyond its usual stop signal." }, "inframe_deletion": { "clinical_label": "Protein-altering", "patient_phrase": "This change removes one or more amino acids without shifting the reading frame." }, "inframe_insertion": { "clinical_label": "Protein-altering", "patient_phrase": "This change inserts one or more amino acids without shifting the reading frame." }, "synonymous_variant": { "clinical_label": "Typically not protein-altering", "patient_phrase": "This change does not alter the amino acid sequence, though some such variants can still affect gene function in specific contexts." }, "non_coding_transcript_variant": { "clinical_label": "Non-coding", "patient_phrase": "This change lies outside the protein-coding sequence and usually requires additional evidence before clinical interpretation." }, "intron_variant": { "clinical_label": "Intronic", "patient_phrase": "This change lies within an intron and usually requires additional evidence before clinical interpretation." }, "whole_gene_deletion": { "clinical_label": "Copy loss", "patient_phrase": "This finding suggests loss of all or most of the gene." }, "whole_gene_duplication": { "clinical_label": "Copy gain", "patient_phrase": "This finding suggests gain of all or most of the gene." }, "exonic_partial_loss": { "clinical_label": "Copy loss", "patient_phrase": "This finding suggests loss affecting part of the gene or one or more exons." }, "exonic_partial_gain": { "clinical_label": "Copy gain", "patient_phrase": "This finding suggests gain affecting part of the gene or one or more exons." } }, "filter_reason_phrases": { "low_quality": "This event did not meet quality thresholds for reporting.", "insufficient_gene_overlap": "This event did not affect enough of the gene or relevant exons to meet reporting criteria.", "broad_nonspecific_cnv": "This was a broad copy-number change and was not considered specific enough for reporting.", "noncoding_no_exact_clinvar_match": "This non-coding finding did not have a sufficiently specific pathogenic reference match for reporting.", "benign_or_not_actionable": "This finding was not considered clinically actionable.", "manual_review_only": "This finding has been retained for manual review rather than automatic reporting." }, "structural_event_templates": { "deletion": { "short_label": "Deletion", "patient_phrase": "A missing DNA segment was identified." }, "duplication": { "short_label": "Duplication", "patient_phrase": "An extra copy of a DNA segment was identified." }, "copy_number_loss": { "short_label": "Copy-number loss", "patient_phrase": "A copy-number loss affecting genomic material was identified." }, "copy_number_gain": { "short_label": "Copy-number gain", "patient_phrase": "A copy-number gain affecting genomic material was identified." }, "partial_exon_deletion": { "short_label": "Partial exon deletion", "patient_phrase": "A deletion affecting part of one or more exons was identified." }, "whole_gene_deletion": { "short_label": "Whole-gene deletion", "patient_phrase": "A deletion affecting all or most of the gene was identified." }, "partial_exon_duplication": { "short_label": "Partial exon duplication", "patient_phrase": "A duplication affecting part of one or more exons was identified." }, "whole_gene_duplication": { "short_label": "Whole-gene duplication", "patient_phrase": "A duplication affecting all or most of the gene was identified." } }, "disease_definitions": [ { "disease_code": "HBOC_BRCA2_PALB2", "display_name": "Hereditary breast, ovarian, pancreatic, prostate and related cancer predisposition", "short_name": "HBOC-related predisposition", "summary": "Inherited pathogenic variants in BRCA2 or PALB2 can increase the risk of several cancers, especially breast cancer, and may also be associated with ovarian, pancreatic, prostate, and related cancer predisposition.", "genes": ["BRCA2", "PALB2"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "HBOC_BRCA1", "display_name": "Hereditary breast and ovarian cancer syndrome", "short_name": "HBOC", "summary": "Inherited pathogenic variants in BRCA1 are associated with substantially increased risk of breast and ovarian cancer and may also increase the risk of other cancers.", "genes": ["BRCA1"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "FAP_APC", "display_name": "Familial adenomatous polyposis", "short_name": "FAP", "summary": "APC-associated familial adenomatous polyposis causes markedly increased risk of multiple colorectal adenomas and colorectal cancer predisposition.", "genes": ["APC"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "FMTC_RET", "display_name": "Familial medullary thyroid carcinoma", "short_name": "FMTC", "summary": "Inherited activating variants in RET are associated with medullary thyroid carcinoma predisposition and may occur within the multiple endocrine neoplasia spectrum.", "genes": ["RET"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "PGL_PCC", "display_name": "Hereditary paraganglioma-pheochromocytoma syndrome", "short_name": "PGL/PCC", "summary": "Pathogenic variants in susceptibility genes such as SDHB, SDHC, SDHD, SDHAF2, MAX, or TMEM127 are associated with inherited risk of paraganglioma and pheochromocytoma.", "genes": ["MAX", "SDHAF2", "SDHB", "SDHC", "SDHD", "TMEM127"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited tumour risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "JPS", "display_name": "Juvenile polyposis syndrome", "short_name": "JPS", "summary": "Pathogenic variants in BMPR1A or SMAD4 are associated with juvenile polyposis syndrome and increased gastrointestinal polyp and cancer risk.", "genes": ["BMPR1A", "SMAD4"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "LFS", "display_name": "Li-Fraumeni syndrome", "short_name": "LFS", "summary": "TP53-associated Li-Fraumeni syndrome confers a broad inherited predisposition to several early-onset cancers.", "genes": ["TP53"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "LYNCH", "display_name": "Lynch syndrome", "short_name": "Lynch syndrome", "summary": "Pathogenic variants in mismatch repair genes such as MLH1, MSH2, MSH6, and PMS2 are associated with inherited colorectal, endometrial, and other cancer risk.", "genes": ["MLH1", "MSH2", "MSH6", "PMS2"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "MAP", "display_name": "MUTYH-associated polyposis", "short_name": "MAP", "summary": "Biallelic pathogenic variants in MUTYH are associated with MUTYH-associated polyposis and increased colorectal cancer risk. A single pathogenic variant is generally interpreted as carrier status in this panel context.", "genes": ["MUTYH"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "MEN1", "display_name": "Multiple endocrine neoplasia type 1", "short_name": "MEN1", "summary": "Pathogenic variants in MEN1 are associated with multiple endocrine neoplasia type 1 and endocrine tumour predisposition.", "genes": ["MEN1"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited tumour risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "MEN2_RET", "display_name": "Multiple endocrine neoplasia type 2", "short_name": "MEN2", "summary": "Activating RET variants are associated with multiple endocrine neoplasia type 2, including medullary thyroid carcinoma and related endocrine tumour risk.", "genes": ["RET"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited tumour risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "NF2", "display_name": "Neurofibromatosis type 2-related schwannomatosis", "short_name": "NF2-related schwannomatosis", "summary": "Pathogenic variants in NF2 are associated with vestibular schwannomas and other nervous system tumours.", "genes": ["NF2"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited tumour risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "PHTS", "display_name": "PTEN hamartoma tumour syndrome", "short_name": "PHTS", "summary": "Pathogenic variants in PTEN are associated with hamartoma syndromes and increased risk of several cancers.", "genes": ["PTEN"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "PJS", "display_name": "Peutz-Jeghers syndrome", "short_name": "PJS", "summary": "Pathogenic variants in STK11 are associated with Peutz-Jeghers syndrome and increased gastrointestinal and extra-intestinal cancer risk.", "genes": ["STK11"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "PILOMATRIXOMA_MUTYH", "display_name": "Pilomatrixoma susceptibility", "short_name": "Pilomatrixoma susceptibility", "summary": "Pilomatrixoma has been reported in association with MUTYH-related disease contexts. Interpretation remains gene and variant dependent.", "genes": ["MUTYH"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding may be relevant to inherited tumour susceptibility.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "RB1", "display_name": "Retinoblastoma predisposition", "short_name": "Retinoblastoma", "summary": "Pathogenic variants in RB1 are associated with hereditary retinoblastoma and increased risk of additional tumours.", "genes": ["RB1"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited tumour risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "TSC", "display_name": "Tuberous sclerosis complex", "short_name": "TSC", "summary": "Pathogenic variants in TSC1 or TSC2 are associated with tuberous sclerosis complex and tumour predisposition involving multiple organs.", "genes": ["TSC1", "TSC2"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with inherited tumour susceptibility.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "WT1", "display_name": "WT1-related Wilms tumour predisposition", "short_name": "WT1-related tumour predisposition", "summary": "Pathogenic variants in WT1 can be associated with Wilms tumour predisposition and related developmental syndromes.", "genes": ["WT1"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with inherited tumour susceptibility.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "VHL", "display_name": "von Hippel-Lindau syndrome", "short_name": "VHL syndrome", "summary": "Pathogenic variants in VHL are associated with inherited susceptibility to several benign and malignant tumours.", "genes": ["VHL"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with inherited tumour susceptibility.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "HBOC_MODERATE_RISK", "display_name": "Hereditary breast and related cancer predisposition", "short_name": "Breast cancer predisposition", "summary": "Pathogenic variants in moderate-risk susceptibility genes such as ATM or CHEK2 can be associated with inherited breast cancer risk.", "genes": ["ATM", "CHEK2"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "OVARIAN_DNA_REPAIR", "display_name": "Hereditary ovarian and related cancer predisposition", "short_name": "Ovarian cancer predisposition", "summary": "Pathogenic variants in genes such as BRIP1, RAD51C, or RAD51D are associated with inherited ovarian and related cancer predisposition.", "genes": ["BRIP1", "RAD51C", "RAD51D"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "HEREDITARY_PROSTATE_CANCER", "display_name": "Hereditary prostate cancer predisposition", "short_name": "Hereditary prostate cancer", "summary": "Pathogenic variants in genes such as HOXB13, ATM, or CHEK2 can be associated with inherited prostate cancer predisposition.", "genes": ["HOXB13", "ATM", "CHEK2"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "FAMILIAL_MELANOMA", "display_name": "Familial melanoma / skin cancer predisposition", "short_name": "Familial melanoma", "summary": "Pathogenic variants in genes such as CDKN2A or CDK4 are associated with familial melanoma predisposition.", "genes": ["CDKN2A", "CDK4"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with inherited tumour susceptibility.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "BAP1_TPDS", "display_name": "BAP1 tumour predisposition syndrome", "short_name": "BAP1-TPDS", "summary": "Pathogenic variants in BAP1 are associated with tumour predisposition that can include melanoma and renal tumours.", "genes": ["BAP1"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with inherited tumour susceptibility.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "BHD", "display_name": "Birt-Hogg-Dube syndrome", "short_name": "BHD", "summary": "Pathogenic variants in FLCN are associated with Birt-Hogg-Dube syndrome and inherited renal tumour susceptibility.", "genes": ["FLCN"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with inherited tumour susceptibility.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "FH_TPDS", "display_name": "FH tumour predisposition syndrome", "short_name": "FH-related tumour predisposition", "summary": "Pathogenic variants in FH are associated with tumour predisposition that can include renal tumours.", "genes": ["FH"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with inherited tumour susceptibility.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "HPRC_MET", "display_name": "Hereditary papillary renal carcinoma", "short_name": "HPRC", "summary": "Activating pathogenic variants in MET are associated with hereditary papillary renal carcinoma.", "genes": ["MET"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with inherited tumour susceptibility.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "LYNCH_EPCAM", "display_name": "Lynch syndrome due to EPCAM-associated MSH2 silencing", "short_name": "EPCAM-associated Lynch syndrome", "summary": "Qualifying EPCAM deletions can be associated with Lynch syndrome through MSH2 epigenetic silencing.", "genes": ["EPCAM"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "PPAP", "display_name": "Polymerase proofreading-associated polyposis", "short_name": "PPAP", "summary": "Pathogenic variants in POLE or POLD1 can be associated with adenomatous polyposis and colorectal cancer predisposition.", "genes": ["POLE", "POLD1"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "NTHL1_TS", "display_name": "NTHL1 tumour syndrome", "short_name": "NTHL1 tumour syndrome", "summary": "Biallelic pathogenic variants in NTHL1 are associated with tumour syndrome involving colorectal polyposis and colorectal cancer risk.", "genes": ["NTHL1"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." }, { "disease_code": "AXIN2_CRC", "display_name": "AXIN2-related colorectal cancer predisposition", "short_name": "AXIN2-related predisposition", "summary": "Pathogenic variants in AXIN2 can be associated with colorectal neoplasia predisposition.", "genes": ["AXIN2"], "category": "Cancer Predisposition", "default_positive_phrase": "This finding is associated with increased inherited cancer risk.", "default_negative_phrase": "No clinically significant finding was identified for this condition." } ], "diseases": [ { "disease": "Hereditary breast, ovarian, pancreatic, prostate and related cancer predisposition", "genes": ["BRCA2", "PALB2"] }, { "disease": "Hereditary breast and ovarian cancer syndrome", "genes": ["BRCA1"] }, { "disease": "Familial adenomatous polyposis", "genes": ["APC"] }, { "disease": "Familial medullary thyroid carcinoma", "genes": ["RET"] }, { "disease": "Hereditary paraganglioma-pheochromocytoma syndrome", "genes": ["MAX", "SDHAF2", "SDHB", "SDHC", "SDHD", "TMEM127"] }, { "disease": "Juvenile polyposis syndrome", "genes": ["BMPR1A", "SMAD4"] }, { "disease": "Li-Fraumeni syndrome", "genes": ["TP53"] }, { "disease": "Lynch syndrome", "genes": ["MLH1", "MSH2", "MSH6", "PMS2"] }, { "disease": "MUTYH-associated polyposis", "genes": ["MUTYH"] }, { "disease": "Multiple endocrine neoplasia type 1", "genes": ["MEN1"] }, { "disease": "Multiple endocrine neoplasia type 2", "genes": ["RET"] }, { "disease": "Neurofibromatosis type 2-related schwannomatosis", "genes": ["NF2"] }, { "disease": "PTEN hamartoma tumour syndrome", "genes": ["PTEN"] }, { "disease": "Peutz-Jeghers syndrome", "genes": ["STK11"] }, { "disease": "Pilomatrixoma susceptibility", "genes": ["MUTYH"] }, { "disease": "Retinoblastoma predisposition", "genes": ["RB1"] }, { "disease": "Tuberous sclerosis complex", "genes": ["TSC1", "TSC2"] }, { "disease": "WT1-related Wilms tumour predisposition", "genes": ["WT1"] }, { "disease": "von Hippel-Lindau syndrome", "genes": ["VHL"] }, { "disease": "Hereditary breast and related cancer predisposition", "genes": ["ATM", "CHEK2"] }, { "disease": "Hereditary ovarian and related cancer predisposition", "genes": ["BRIP1", "RAD51C", "RAD51D"] }, { "disease": "Hereditary prostate cancer predisposition", "genes": ["HOXB13", "ATM", "CHEK2"] }, { "disease": "Familial melanoma / skin cancer predisposition", "genes": ["CDKN2A", "CDK4"] }, { "disease": "BAP1 tumour predisposition syndrome", "genes": ["BAP1"] }, { "disease": "Birt-Hogg-Dube syndrome", "genes": ["FLCN"] }, { "disease": "FH tumour predisposition syndrome", "genes": ["FH"] }, { "disease": "Hereditary papillary renal carcinoma", "genes": ["MET"] }, { "disease": "Lynch syndrome due to EPCAM-associated MSH2 silencing", "genes": ["EPCAM"] }, { "disease": "Polymerase proofreading-associated polyposis", "genes": ["POLE", "POLD1"] }, { "disease": "NTHL1 tumour syndrome", "genes": ["NTHL1"] }, { "disease": "AXIN2-related colorectal cancer predisposition", "genes": ["AXIN2"] } ], "gene_report_metadata": { "APC": { "gene": "APC", "display_name": "APC", "full_name": "adenomatous polyposis coli", "short_role": "Tumour suppressor that helps regulate cell growth and the Wnt signalling pathway.", "associated_condition_summary": "FAP", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in APC may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["FAP_APC"], "organ_system": "Cancer Predisposition", "sort_order": 10, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "BMPR1A": { "gene": "BMPR1A", "display_name": "BMPR1A", "full_name": "bone morphogenetic protein receptor type 1A", "short_role": "Receptor in the TGF-beta/BMP pathway involved in growth control and tissue development.", "associated_condition_summary": "Juvenile polyposis syndrome", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in BMPR1A may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["JPS"], "organ_system": "Cancer Predisposition", "sort_order": 20, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "BRCA1": { "gene": "BRCA1", "display_name": "BRCA1", "full_name": "BRCA1 DNA repair associated", "short_role": "Helps repair double-strand DNA damage and maintain genomic stability.", "associated_condition_summary": "Hereditary breast and ovarian cancer predisposition", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in BRCA1 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["HBOC_BRCA1"], "organ_system": "Cancer Predisposition", "sort_order": 30, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "BRCA2": { "gene": "BRCA2", "display_name": "BRCA2", "full_name": "BRCA2 DNA repair associated", "short_role": "Helps repair DNA through homologous recombination and works closely with PALB2.", "associated_condition_summary": "Hereditary breast and ovarian cancer predisposition", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in BRCA2 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["HBOC_BRCA2_PALB2"], "organ_system": "Cancer Predisposition", "sort_order": 40, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "MAX": { "gene": "MAX", "display_name": "MAX", "full_name": "MYC associated factor X", "short_role": "Regulates gene transcription and cell growth as part of the MYC-MAX-MXD network.", "associated_condition_summary": "Hereditary paraganglioma-pheochromocytoma", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in MAX may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["PGL_PCC"], "organ_system": "Cancer Predisposition", "sort_order": 50, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "MEN1": { "gene": "MEN1", "display_name": "MEN1", "full_name": "menin 1", "short_role": "Tumour suppressor involved in transcriptional regulation, genome stability, and endocrine cell growth control.", "associated_condition_summary": "Multiple endocrine neoplasia type 1", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in MEN1 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["MEN1"], "organ_system": "Cancer Predisposition", "sort_order": 60, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "MLH1": { "gene": "MLH1", "display_name": "MLH1", "full_name": "MutL homolog 1", "short_role": "Core DNA mismatch repair protein that helps correct replication errors.", "associated_condition_summary": "Lynch syndrome", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in MLH1 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["LYNCH"], "organ_system": "Cancer Predisposition", "sort_order": 70, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "MSH2": { "gene": "MSH2", "display_name": "MSH2", "full_name": "MutS homolog 2", "short_role": "Core DNA mismatch repair protein that recognises base-pair mismatches and small insertion-deletion loops.", "associated_condition_summary": "Lynch syndrome", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in MSH2 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["LYNCH"], "organ_system": "Cancer Predisposition", "sort_order": 80, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "MSH6": { "gene": "MSH6", "display_name": "MSH6", "full_name": "MutS homolog 6", "short_role": "DNA mismatch repair protein that partners with MSH2 to detect replication errors.", "associated_condition_summary": "Lynch syndrome", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in MSH6 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["LYNCH"], "organ_system": "Cancer Predisposition", "sort_order": 90, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "MUTYH": { "gene": "MUTYH", "display_name": "MUTYH", "full_name": "mutY DNA glycosylase", "short_role": "Base-excision repair glycosylase that helps correct oxidative DNA damage.", "associated_condition_summary": "MUTYH-associated polyposis", "inheritance_mode": "autosomal_recessive", "default_result_label": "Carrier", "patient_friendly_summary": "A clinically significant finding in MUTYH may indicate carrier status or, if pathogenic variants are present on both alleles, MUTYH-associated polyposis.", "default_condition_codes": ["MAP", "PILOMATRIXOMA_MUTYH"], "organ_system": "Cancer Predisposition", "sort_order": 100, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "NF2": { "gene": "NF2", "display_name": "NF2", "full_name": "neurofibromin 2", "short_role": "Tumour suppressor that helps regulate cell contact signalling and Schwann cell growth.", "associated_condition_summary": "Neurofibromatosis type 2-related schwannomatosis", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in NF2 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["NF2"], "organ_system": "Cancer Predisposition", "sort_order": 110, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "PALB2": { "gene": "PALB2", "display_name": "PALB2", "full_name": "partner and localizer of BRCA2", "short_role": "Links BRCA1 and BRCA2 and supports homologous recombination DNA repair.", "associated_condition_summary": "Hereditary breast cancer predisposition", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in PALB2 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["HBOC_BRCA2_PALB2"], "organ_system": "Cancer Predisposition", "sort_order": 120, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "PMS2": { "gene": "PMS2", "display_name": "PMS2", "full_name": "PMS1 homolog 2, mismatch repair system component", "short_role": "DNA mismatch repair protein that partners with MLH1 to correct replication errors.", "associated_condition_summary": "Lynch syndrome", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in PMS2 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["LYNCH"], "organ_system": "Cancer Predisposition", "sort_order": 130, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "PTEN": { "gene": "PTEN", "display_name": "PTEN", "full_name": "phosphatase and tensin homolog", "short_role": "Tumour suppressor that negatively regulates PI3K-AKT signalling.", "associated_condition_summary": "PTEN hamartoma tumour syndrome", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in PTEN may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["PHTS"], "organ_system": "Cancer Predisposition", "sort_order": 140, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "RB1": { "gene": "RB1", "display_name": "RB1", "full_name": "RB transcriptional corepressor 1", "short_role": "Key cell-cycle tumour suppressor controlling progression through the G1/S checkpoint.", "associated_condition_summary": "Retinoblastoma predisposition", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in RB1 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["RB1"], "organ_system": "Cancer Predisposition", "sort_order": 150, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "RET": { "gene": "RET", "display_name": "RET", "full_name": "RET proto-oncogene", "short_role": "Receptor tyrosine kinase involved in neural crest and endocrine cell signalling.", "associated_condition_summary": "Multiple endocrine neoplasia and medullary thyroid carcinoma", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant activating change in RET may be associated with inherited medullary thyroid carcinoma or multiple endocrine neoplasia type 2.", "default_condition_codes": ["FMTC_RET", "MEN2_RET"], "organ_system": "Cancer Predisposition", "sort_order": 160, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "SDHAF2": { "gene": "SDHAF2", "display_name": "SDHAF2", "full_name": "succinate dehydrogenase complex assembly factor 2", "short_role": "Supports assembly of mitochondrial complex II and cellular energy metabolism.", "associated_condition_summary": "Hereditary paraganglioma-pheochromocytoma", "inheritance_mode": "autosomal_dominant_parent_of_origin_effect", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in SDHAF2 may be associated with inherited paraganglioma susceptibility. Parent-of-origin effects may matter clinically.", "default_condition_codes": ["PGL_PCC"], "organ_system": "Cancer Predisposition", "sort_order": 170, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "SDHB": { "gene": "SDHB", "display_name": "SDHB", "full_name": "succinate dehydrogenase complex iron sulfur subunit B", "short_role": "Mitochondrial complex II subunit involved in oxidative phosphorylation and tumour suppression.", "associated_condition_summary": "Hereditary paraganglioma-pheochromocytoma", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in SDHB may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["PGL_PCC"], "organ_system": "Cancer Predisposition", "sort_order": 180, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "SDHC": { "gene": "SDHC", "display_name": "SDHC", "full_name": "succinate dehydrogenase complex subunit C", "short_role": "Mitochondrial complex II membrane subunit involved in cellular respiration.", "associated_condition_summary": "Hereditary paraganglioma-pheochromocytoma", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in SDHC may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["PGL_PCC"], "organ_system": "Cancer Predisposition", "sort_order": 190, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "SDHD": { "gene": "SDHD", "display_name": "SDHD", "full_name": "succinate dehydrogenase complex subunit D", "short_role": "Mitochondrial complex II membrane subunit involved in cellular respiration.", "associated_condition_summary": "Hereditary paraganglioma-pheochromocytoma", "inheritance_mode": "autosomal_dominant_parent_of_origin_effect", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in SDHD may be associated with inherited paraganglioma susceptibility. Parent-of-origin effects may matter clinically.", "default_condition_codes": ["PGL_PCC"], "organ_system": "Cancer Predisposition", "sort_order": 200, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "SMAD4": { "gene": "SMAD4", "display_name": "SMAD4", "full_name": "SMAD family member 4", "short_role": "Central mediator of TGF-beta signalling involved in growth control and tissue homeostasis.", "associated_condition_summary": "Juvenile polyposis syndrome", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in SMAD4 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["JPS"], "organ_system": "Cancer Predisposition", "sort_order": 210, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "STK11": { "gene": "STK11", "display_name": "STK11", "full_name": "serine/threonine kinase 11", "short_role": "Tumour suppressor kinase involved in cell polarity, metabolism, and growth control.", "associated_condition_summary": "Peutz-Jeghers syndrome", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in STK11 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["PJS"], "organ_system": "Cancer Predisposition", "sort_order": 220, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "TMEM127": { "gene": "TMEM127", "display_name": "TMEM127", "full_name": "transmembrane protein 127", "short_role": "Negative regulator of mTOR signalling associated with endocrine tumour susceptibility.", "associated_condition_summary": "Hereditary paraganglioma-pheochromocytoma", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in TMEM127 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["PGL_PCC"], "organ_system": "Cancer Predisposition", "sort_order": 230, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "TP53": { "gene": "TP53", "display_name": "TP53", "full_name": "tumour protein p53", "short_role": "Master tumour suppressor that coordinates DNA-damage responses, cell-cycle arrest, and apoptosis.", "associated_condition_summary": "Li-Fraumeni syndrome", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in TP53 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["LFS"], "organ_system": "Cancer Predisposition", "sort_order": 240, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "TSC1": { "gene": "TSC1", "display_name": "TSC1", "full_name": "TSC complex subunit 1", "short_role": "Forms part of the TSC1-TSC2 complex that restrains mTOR signalling.", "associated_condition_summary": "Tuberous sclerosis complex", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in TSC1 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["TSC"], "organ_system": "Cancer Predisposition", "sort_order": 250, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "TSC2": { "gene": "TSC2", "display_name": "TSC2", "full_name": "TSC complex subunit 2", "short_role": "Forms part of the TSC1-TSC2 complex that restrains mTOR signalling.", "associated_condition_summary": "Tuberous sclerosis complex", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in TSC2 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["TSC"], "organ_system": "Cancer Predisposition", "sort_order": 260, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "VHL": { "gene": "VHL", "display_name": "VHL", "full_name": "von Hippel-Lindau tumour suppressor", "short_role": "Tumour suppressor involved in oxygen-sensing and degradation of HIF proteins.", "associated_condition_summary": "von Hippel-Lindau syndrome", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in VHL may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["VHL"], "organ_system": "Cancer Predisposition", "sort_order": 270, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "WT1": { "gene": "WT1", "display_name": "WT1", "full_name": "Wilms tumour 1", "short_role": "Transcription factor important in kidney and gonadal development.", "associated_condition_summary": "WT1-related tumour predisposition", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in WT1 may be associated with inherited cancer or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["WT1"], "organ_system": "Cancer Predisposition", "sort_order": 280, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "ATM": { "gene": "ATM", "display_name": "ATM", "full_name": "ATM serine/threonine kinase", "short_role": "DNA damage response kinase involved in double-strand break signalling and genome stability.", "associated_condition_summary": "Hereditary breast and related cancer predisposition", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in ATM may be associated with inherited cancer susceptibility, depending on the finding and context.", "default_condition_codes": [ "HBOC_MODERATE_RISK", "HEREDITARY_PROSTATE_CANCER" ], "organ_system": "Cancer Predisposition", "sort_order": 290, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "CHEK2": { "gene": "CHEK2", "display_name": "CHEK2", "full_name": "checkpoint kinase 2", "short_role": "DNA damage checkpoint kinase that helps coordinate cell-cycle arrest and DNA repair.", "associated_condition_summary": "Hereditary breast and related cancer predisposition", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in CHEK2 may be associated with inherited cancer susceptibility, depending on the finding and context.", "default_condition_codes": [ "HBOC_MODERATE_RISK", "HEREDITARY_PROSTATE_CANCER" ], "organ_system": "Cancer Predisposition", "sort_order": 300, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "BRIP1": { "gene": "BRIP1", "display_name": "BRIP1", "full_name": "BRCA1 interacting helicase 1", "short_role": "DNA helicase involved in homologous recombination and DNA interstrand cross-link repair.", "associated_condition_summary": "Hereditary ovarian and related cancer predisposition", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in BRIP1 may be associated with inherited cancer susceptibility, depending on the finding and context.", "default_condition_codes": ["OVARIAN_DNA_REPAIR"], "organ_system": "Cancer Predisposition", "sort_order": 310, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "RAD51C": { "gene": "RAD51C", "display_name": "RAD51C", "full_name": "RAD51 paralog C", "short_role": "Homologous recombination repair protein involved in DNA double-strand break repair.", "associated_condition_summary": "Hereditary ovarian and related cancer predisposition", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in RAD51C may be associated with inherited cancer susceptibility, depending on the finding and context.", "default_condition_codes": ["OVARIAN_DNA_REPAIR"], "organ_system": "Cancer Predisposition", "sort_order": 320, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "RAD51D": { "gene": "RAD51D", "display_name": "RAD51D", "full_name": "RAD51 paralog D", "short_role": "Homologous recombination repair protein involved in maintenance of genomic stability.", "associated_condition_summary": "Hereditary ovarian and related cancer predisposition", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in RAD51D may be associated with inherited cancer susceptibility, depending on the finding and context.", "default_condition_codes": ["OVARIAN_DNA_REPAIR"], "organ_system": "Cancer Predisposition", "sort_order": 330, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "HOXB13": { "gene": "HOXB13", "display_name": "HOXB13", "full_name": "homeobox B13", "short_role": "Transcription factor involved in prostate development and androgen-regulated pathways.", "associated_condition_summary": "Hereditary prostate cancer predisposition", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in HOXB13 may be associated with inherited prostate cancer susceptibility, depending on the finding and context.", "default_condition_codes": ["HEREDITARY_PROSTATE_CANCER"], "organ_system": "Cancer Predisposition", "sort_order": 340, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "CDKN2A": { "gene": "CDKN2A", "display_name": "CDKN2A", "full_name": "cyclin dependent kinase inhibitor 2A", "short_role": "Tumour suppressor involved in cell-cycle control through p16INK4A and p14ARF pathways.", "associated_condition_summary": "Familial melanoma", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in CDKN2A may be associated with inherited melanoma or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["FAMILIAL_MELANOMA"], "organ_system": "Cancer Predisposition", "sort_order": 350, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "CDK4": { "gene": "CDK4", "display_name": "CDK4", "full_name": "cyclin dependent kinase 4", "short_role": "Cell-cycle kinase that promotes G1-to-S phase progression.", "associated_condition_summary": "Familial melanoma", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in CDK4 may be associated with inherited melanoma or tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["FAMILIAL_MELANOMA"], "organ_system": "Cancer Predisposition", "sort_order": 360, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "BAP1": { "gene": "BAP1", "display_name": "BAP1", "full_name": "BRCA1 associated protein 1", "short_role": "Deubiquitinating tumour suppressor involved in chromatin regulation, DNA damage response, and cell growth control.", "associated_condition_summary": "BAP1 tumour predisposition syndrome", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in BAP1 may be associated with inherited melanoma, renal, or other tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["BAP1_TPDS"], "organ_system": "Cancer Predisposition", "sort_order": 370, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "FLCN": { "gene": "FLCN", "display_name": "FLCN", "full_name": "folliculin", "short_role": "Tumour suppressor involved in nutrient sensing, mTOR-related signalling, and renal tumour biology.", "associated_condition_summary": "Birt-Hogg-Dube syndrome", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in FLCN may be associated with inherited renal tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["BHD"], "organ_system": "Cancer Predisposition", "sort_order": 380, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "FH": { "gene": "FH", "display_name": "FH", "full_name": "fumarate hydratase", "short_role": "Tricarboxylic acid cycle enzyme with tumour suppressor roles in cellular metabolism.", "associated_condition_summary": "FH tumour predisposition syndrome", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in FH may be associated with inherited renal or other tumour susceptibility, depending on the finding and context.", "default_condition_codes": ["FH_TPDS"], "organ_system": "Cancer Predisposition", "sort_order": 390, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "MET": { "gene": "MET", "display_name": "MET", "full_name": "MET proto-oncogene, receptor tyrosine kinase", "short_role": "Receptor tyrosine kinase involved in growth, motility, and invasive signalling pathways.", "associated_condition_summary": "Hereditary papillary renal carcinoma", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant activating change in MET may be associated with inherited papillary renal carcinoma, depending on the finding and context.", "default_condition_codes": ["HPRC_MET"], "organ_system": "Cancer Predisposition", "sort_order": 400, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "EPCAM": { "gene": "EPCAM", "display_name": "EPCAM", "full_name": "epithelial cell adhesion molecule", "short_role": "Cell adhesion protein; qualifying 3-prime deletions can lead to MSH2 silencing in Lynch syndrome.", "associated_condition_summary": "EPCAM-associated Lynch syndrome", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A qualifying EPCAM finding may be associated with inherited colorectal cancer susceptibility, depending on the finding and context.", "default_condition_codes": ["LYNCH_EPCAM"], "organ_system": "Cancer Predisposition", "sort_order": 410, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "POLE": { "gene": "POLE", "display_name": "POLE", "full_name": "DNA polymerase epsilon catalytic subunit", "short_role": "Replicative DNA polymerase with proofreading activity important for genome fidelity.", "associated_condition_summary": "Polymerase proofreading-associated polyposis", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in POLE may be associated with inherited colorectal cancer or polyposis susceptibility, depending on the finding and context.", "default_condition_codes": ["PPAP"], "organ_system": "Cancer Predisposition", "sort_order": 420, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "POLD1": { "gene": "POLD1", "display_name": "POLD1", "full_name": "DNA polymerase delta 1 catalytic subunit", "short_role": "Replicative DNA polymerase with proofreading activity important for genome fidelity.", "associated_condition_summary": "Polymerase proofreading-associated polyposis", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in POLD1 may be associated with inherited colorectal cancer or polyposis susceptibility, depending on the finding and context.", "default_condition_codes": ["PPAP"], "organ_system": "Cancer Predisposition", "sort_order": 430, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "NTHL1": { "gene": "NTHL1", "display_name": "NTHL1", "full_name": "Nth like DNA glycosylase 1", "short_role": "Base-excision repair glycosylase involved in repair of oxidised DNA bases.", "associated_condition_summary": "NTHL1 tumour syndrome", "inheritance_mode": "autosomal_recessive", "default_result_label": "Carrier", "patient_friendly_summary": "A clinically significant finding in NTHL1 may indicate carrier status or, if pathogenic variants are present on both alleles, NTHL1 tumour syndrome.", "default_condition_codes": ["NTHL1_TS"], "organ_system": "Cancer Predisposition", "sort_order": 440, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null }, "AXIN2": { "gene": "AXIN2", "display_name": "AXIN2", "full_name": "axin 2", "short_role": "Wnt pathway regulator involved in beta-catenin signalling and colorectal epithelial homeostasis.", "associated_condition_summary": "AXIN2-related colorectal cancer predisposition", "inheritance_mode": "autosomal_dominant", "default_result_label": "High Risk", "patient_friendly_summary": "A clinically significant change in AXIN2 may be associated with inherited colorectal neoplasia susceptibility, depending on the finding and context.", "default_condition_codes": ["AXIN2_CRC"], "organ_system": "Cancer Predisposition", "sort_order": 450, "preferred_transcript": null, "preferred_transcript_source": "ensembl_canonical_or_primary_protein_coding", "chromosome": null, "start": null, "end": null, "length": null, "strand": null, "ensembl_gene_id": null } }, "gene_rules": { "MUTYH": { "inheritance_mode": "autosomal_recessive", "single_allele_interpretation": "carrier", "biallelic_interpretation": "positive", "noncoding_exact_clinvar_policy": "manual_review", "snippets": { "positive_biallelic": "Biallelic-compatible pathogenic small variant finding identified", "carrier_single": "Single actionable MUTYH finding identified; carrier-level interpretation unless second pathogenic allele is present", "review_biallelic": "Exact ClinVar pathogenic MUTYH match identified in a biallelic-compatible state; manual review required", "review_single": "Exact ClinVar pathogenic MUTYH match identified; manual review required before carrier-level interpretation" } }, "SDHD": { "inheritance_mode": "autosomal_dominant_parent_of_origin_effect", "special_note": "Clinical interpretation may depend on parent-of-origin context." }, "SDHAF2": { "inheritance_mode": "autosomal_dominant_parent_of_origin_effect", "special_note": "Clinical interpretation may depend on parent-of-origin context." }, "NTHL1": { "inheritance_mode": "autosomal_recessive", "single_allele_interpretation": "carrier", "biallelic_interpretation": "positive", "noncoding_exact_clinvar_policy": "manual_review", "snippets": { "positive_biallelic": "Biallelic-compatible pathogenic small variant finding identified", "carrier_single": "Single actionable NTHL1 finding identified; carrier-level interpretation unless second pathogenic allele is present", "review_biallelic": "Exact ClinVar pathogenic NTHL1 match identified in a biallelic-compatible state; manual review required", "review_single": "Exact ClinVar pathogenic NTHL1 match identified; manual review required before carrier-level interpretation" } }, "EPCAM": { "inheritance_mode": "autosomal_dominant", "special_note": "For Lynch syndrome, only qualifying EPCAM deletions involving the 3-prime region with MSH2 silencing should be treated as causative; isolated small variants are not automatically treated as Lynch-causative." }, "POLE": { "inheritance_mode": "autosomal_dominant", "special_note": "Polymerase proofreading-associated polyposis is most classically associated with pathogenic exonuclease-domain variants; broader interpretation should be reviewed carefully." }, "POLD1": { "inheritance_mode": "autosomal_dominant", "special_note": "Polymerase proofreading-associated polyposis is most classically associated with pathogenic exonuclease-domain variants; broader interpretation should be reviewed carefully." }, "MET": { "inheritance_mode": "autosomal_dominant", "special_note": "Hereditary papillary renal carcinoma is classically associated with activating MET variants, often in the tyrosine kinase domain." } }, "display_rules": { "status_order": [ "positive", "carrier", "review", "structural_review", "vus", "negative" ], "finding_type_order": [ "small_variant", "structural_variant", "review_candidate" ], "gene_priority": [ "BRCA1", "BRCA2", "TP53", "PALB2", "ATM", "CHEK2", "HOXB13", "CDKN2A", "BAP1", "MLH1", "MSH2", "MSH6", "PMS2", "EPCAM", "APC", "MUTYH", "NTHL1", "POLE", "POLD1", "AXIN2", "BRIP1", "RAD51C", "RAD51D", "PTEN", "STK11", "RET", "RB1", "VHL", "FLCN", "FH", "MET", "MEN1", "NF2", "TSC1", "TSC2", "SMAD4", "BMPR1A", "WT1", "SDHB", "SDHD", "SDHC", "SDHAF2", "MAX", "TMEM127", "CDK4" ] }, "unique_genes": [ { "gene": "APC" }, { "gene": "ATM" }, { "gene": "AXIN2" }, { "gene": "BAP1" }, { "gene": "BMPR1A" }, { "gene": "BRCA1" }, { "gene": "BRCA2" }, { "gene": "BRIP1" }, { "gene": "CDK4" }, { "gene": "CDKN2A" }, { "gene": "CHEK2" }, { "gene": "EPCAM" }, { "gene": "FH" }, { "gene": "FLCN" }, { "gene": "HOXB13" }, { "gene": "MAX" }, { "gene": "MEN1" }, { "gene": "MET" }, { "gene": "MLH1" }, { "gene": "MSH2" }, { "gene": "MSH6" }, { "gene": "MUTYH" }, { "gene": "NF2" }, { "gene": "NTHL1" }, { "gene": "PALB2" }, { "gene": "PMS2" }, { "gene": "POLD1" }, { "gene": "POLE" }, { "gene": "PTEN" }, { "gene": "RAD51C" }, { "gene": "RAD51D" }, { "gene": "RB1" }, { "gene": "RET" }, { "gene": "SDHAF2" }, { "gene": "SDHB" }, { "gene": "SDHC" }, { "gene": "SDHD" }, { "gene": "SMAD4" }, { "gene": "STK11" }, { "gene": "TMEM127" }, { "gene": "TP53" }, { "gene": "TSC1" }, { "gene": "TSC2" }, { "gene": "VHL" }, { "gene": "WT1" } ] }