Frequency of variants of uncertain significance in BRCA1 and BRCA2 in an Irish cohort.

e13006Background: Screening for germline BRCA1/2 mutations predisposing to hereditary breast ovarian cancer (HBOC) syndrome is complicated by the identification of genetic variants of uncertain significance (VUS). These are often rare missense variants, ranging from harmless polymorphisms to deleterious mutations. VUS’s are considered in pre- and post test counseling, and increasingly encountered due to the uptake of panel testing. We determined the frequency of VUS in an Irish HBOC cohort. Methods: The results of consecutive BRCA1/2 genetic analysis performed in the clinical cancer genetics departments of the Mater Private Hospital and the Mater Misericordiae University Hospital were correlated with personal and family history of cancer and age at diagnosis. Results: 519 individuals (501 females and 18 males) underwent formal genetic counseling and diagnostic BRCA1/2 screening between January 2011 and January 2016. Pathogenic mutations were identified in 57 (10.9%) of the individuals tested, 18 (3.4%) mu...