Clinical Domain Working Groups

Most members of this VCEP are known to ClinGen as representatives of the Evidence-based Network for the Interpretation of Germline Mutation Alleles (ENIGMA) external expert panel for interpretation of variants in BRCA1 and BRCA2, genes for which pathogenic variants predispose carriers to breast, ovarian and other cancer types, including male breast, pancreatic, (high grade) prostate cancer.

Expert Panel classifications performed by ENIGMA up to and including Feb 2020 were based on the previous in-house ENIGMA quantitative and qualitative criteria. The ENIGMA BRCA1 and BRCA2 VCEP is now recognised as an internal ClinGen VCEP, following ClinGen ACMG/AMP guidelines. In discussion with members of the ClinGen SVI subgroup, approved specifications of the ACMG/AMP rules for the classification of variants in the BRCA1 and BRCA2 genes are now available in the ClinGen Criteria Specification Registry. Previous ENIGMA Expert Panel classifications will be removed from ClinVar, as they are revised by the ENIGMA BRCA1 and BRCA2 VCEP, to ensure that only the latest classification is displayed as the Expert Panel assertion.

Committee members represent the ENIGMA consortium for characterisation of variants in breast and ovarian cancer predisposition genes, along with clinical diagnostic and research laboratories from the US and Europe. The committee will also interface with the ClinGen Hereditary Breast Ovarian Pancreatic and other Hereditary Cancer VCEPs, to promote commonality between development and application of gene-specific guidelines for hereditary cancer genes.