<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Pathogenic variants in <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> (<jats:italic>BRCA1/2</jats:italic>) lead to increased risk of breast, ovarian, and other cancers, but most variant-positive individuals in the general population are unaware of their risk, and little is known about prevalence in non-European populations. We investigated <jats:italic>BRCA1/2</jats:italic> prevalence and impact in the electronic health record (EHR)-linked Bio<jats:italic>Me</jats:italic> Biobank in New York City.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Exome sequence data from 30,223 adult Bio<jats:italic>Me</jats:italic> participants were evaluated for pathogenic variants in <jats:italic>BRCA1/2</jats:italic>. Prevalence estimates were made in population groups defined by genetic ancestry and self-report. EHR data were used to evaluate clinical characteristics of variant-positive individuals.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>There were 218 (0.7%) individuals harboring expected pathogenic variants, resulting in an overall prevalence of 1 in 139. The highest prevalence was in individuals with Ashkenazi Jewish (AJ; 1 in 49), Filipino and other Southeast Asian (1 in 81), and non-AJ European (1 in 103) ancestry. Among 218 variant-positive individuals, 112 (51.4%) harbored known founder variants: 80 had AJ founder variants (<jats:italic>BRCA1</jats:italic> c.5266dupC and c.68_69delAG, and <jats:italic>BRCA2</jats:italic> c.5946delT), 8 had a Puerto Rican founder variant (<jats:italic>BRCA2</jats:italic> c.3922G>T), and 24 had one of 19 other founder variants. Non-European populations were more likely to harbor <jats:italic>BRCA1/2</jats:italic> variants that were not classified in ClinVar or that had uncertain or conflicting evidence for pathogenicity (uncertain/conflicting). Within mixed ancestry populations, such as Hispanic/Latinos with genetic ancestry from Africa, Europe, and the Americas, there was a strong correlation between the proportion of African genetic ancestry and the likelihood of harboring an uncertain/conflicting variant. Approximately 28% of variant-positive individuals had a personal history, and 45% had a personal or family history of <jats:italic>BRCA1/2-</jats:italic>associated cancers. Approximately 27% of variant-positive individuals had prior clinical genetic testing for <jats:italic>BRCA1/2</jats:italic>. However, individuals with AJ founder variants were twice as likely to have had a clinical test (39%) than those with other pathogenic variants (20%).</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>These findings deepen our knowledge about <jats:italic>BRCA1/2</jats:italic> variants and associated cancer risk in diverse populations, indicate a gap in knowledge about potential cancer-related variants in non-European populations, and suggest that genomic screening in diverse patient populations may be an effective tool to identify at-risk individuals.</jats:p> </jats:sec>