Genepod 2020 - Classifying variants of unknown significance in BRCA1/BRCA2...

When a variant of unknown significance (VUS) shows up in a genetic test, it's frustrating. Without clinical data backing the pathogenicity of a variant, it is difficult to advise patients. As genetic screening increases, more VUS crop up, and become even harder to classify due to an expanding pool of clinical characteristics of patients. For BRCA1/BRCA2 testing, VUS occur in 2-4% of cases, and the number of VUS that have been identified is roughly equal to the number of pathogenic variants. In a recent publication in GIM, Dr. David Goldgar and his team expanded on their work studying VUS in BRCA1/BRCA2 using clinical genetic tests in 138,000 individuals undergoing genetic testing for hereditary cancer. On this month's GenePod, Dr. Goldgar discusses their new model for predicting pathogenicity of BRCA1/BRCA2 VUS using family history, and the value of grouping similar VUS, rather than studying them individually. Related article link: https://www.nature.com/articles/s41436-019-0729-1