Reclassification of BRCA1 and BRCA2 variants found in ovarian epithelial, fallopian tube, and primary peritoneal cancers

We investigated the proportions of and reclassified variants of unknown significance (VUS) in Korean patients with epithelial ovarian, tubal, and primary peritoneal cancers. Data from 805 patients who underwent genetic testing for from January 1, 2006 to August 31, 2018 were included. The VUS in were reclassified using the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology standards and guidelines. A pathogenic variant was found in 17.0% (137/805) of the patients, and VUS were found in 15.9% (128/805) of the patients. Further, 8.7% (69/805) of the patients possessed a pathogenic variant and 18.4% (148/805) of the patients possessed VUS. Fifty-three specific VUS were found and 20 were further reclassified as benign (n=11), likely benign (n=5), likely pathogenic (n=3), and pathogenic (n=1). The remaining 33 remained classified as VUS. For , 55 specific VUS were detected; among these, 14 were reclassified as benign or likely benign, and 2 were reclassified as likely pathogenic. Among the 805 patients, 195 were found to have only VUS and no pathogenic variants (PV), and 41.5% (81/195) were reclassified as benign or likely benign, and 10.3% (20/195) as pathogenic or likely pathogenic variants. Approximately 33.3% (36/108) of the specific variants analyzed in this study that were initially classified as VUS over a 13-year period were reclassified. Among these, 5.6% (6/108) were reclassified as pathogenic or likely pathogenic variants.