Overall management and deployment of the BRCA Exchange web portal and pipeline scripts
Biomedicine is in transition as genetic testing is becoming the standard of care. A growing number of individuals are now undergoing genetic testing to better understand and manage their risk of disease. This is particularly true of BRCA testing. Women who carry pathogenic BRCA2 variants have an estimated 49% risk of breast cancer and 18% risk of ovarian cancer by the age of 70; the risk for those carrying a BRCA1 variant are worse at 57% and 40% respectively. Pathogenic BRCA variants have been implicated in prostate, pancreatic and stomach cancers, and some variants in these genes can indicate cancer patients who are likely to benefit from treatment with PARP inhibitors. All of these findings have greatly increased the rate at which BRCA testing is performed. As more individuals undergo testing, new genetic variants continue to be observed, however, our ability to detect these variants has outpaced our ability to determine their clinical significance. About one-third of BRCA variants currently in ClinVar are Variants of Uncertain Significance (see https://www.ncbi.nlm.nih.gov/clinvar). And more importantly, all too often, BRCA tests report one or more Variants of Unknown or Uncertain Significance (VUS). While VUS rates vary by test, a common estimate is that roughly 15% of BRCA tests report one or more VUS.
Solving the VUS problem means gathering BRCA variation data from wherever it is available. In 2014, the Global Alliance for Genomics and Health (GA4GH) launched the BRCA Challenge to address the challenges in gathering data from around the globe by focusing first on two important, well-characterized genes, which will ultimately serving as a model for other genes. In 2016, we launched BRCA Exchange (http://brcaexchange.org), the first work product of the BRCA Challenge. BRCA Exchange now combines BRCA variant-level data from ClinVar, LOVD, BIC, ExAC, 1000 Genomes, ESP, exLOVD and ENIGMA into the world’s largest source of non-proprietary BRCA variant-level data. These data have enabled the expert review of thousands of variants.
##Authors Benedict Paten, Charles Markello, Molly Zhang, Max Haeussler, Melissa Cline, Zack Fischmann, Joe Thomas, Brian Craft.