Design and validation of a next generation sequencing assay for hereditary BRCA1 and BRCA2 mutation testing

Hereditary breast and ovarian cancer syndrome, caused by a germline pathogenic variant in the BRCA1 Or BRCA2 (BRCA1/2) genes, is characterized by an increased risk for breast, ovarian, pancreatic and other cancers. Identification of those who have a BRCA1/2 mutation is important so that they can take advantage of genetic counseling, screening, and potentially life-saving prevention strategies. We describe the design and analytic validation of the Counsyl Inherited. Cancer Screen, a next-generation sequencing -based test to detect pathogenic variation the BRCA1 and BRCA2 genes. We demonstrate that the test is capable of detecting single-nucleotide variants (SNVs) short insertions and deletions (indels), and copy-number variants (CNVs, lalso known as large rearrangements) with zero errors over a 114-sample validation set consisting of samples from cell lines and deidentified patient samples, including 36 samples with BRCA1/2 Pathogenic germline mutations.