A recurrent pathogenic BRCA2 exon 5–11 duplication in the Christian Arab population in Israel

Germline pathogenic variants (PVs) in BRCA1/BRCA2 are well-established risk factors for breast cancer (BC) and/or ovarian cancer (OC). Founder PVs have been described in BRCA1 / BRCA2 in several genetic isolates. The Christian Arab population in the Middle East is a relatively isolated ethnic group, yet founder, or recurrent BRCA1/BRCA2 PVs have not been reported in this population. In this study we describe PVs detected in cancer susceptibility genes among a cohort of Christian Arabs from Israel. We reviewed patient records from the Oncogenetic clinic at Rambam Health Care Campus during the years 2013- mid 2020. Thirty-five unrelated Christian Arab patients, with personal or family history of BC and/or OC underwent BRCA1/BRCA2 (14/35) testing or cancer gene panel testing (21/35) as part of their diagnostic workup. Three clinically significant variants in BRCA2, CHEK2 and RAD51C were found in 7/35 patients (20%). A recurrent duplication of the BRCA2 genomic region, encompassing exons 5–10 and the 5' portion of exon 11, was found in 5/33 (15.2%) patients for whom copy number variants (CNVs) analysis was performed. We identified a recurrent pathogenic BRCA2 duplication in Christian Arab patients with a personal/ family history of BC and/or OC. Our findings emphasize the importance of inclusion of CNVs analysis in BRCA1/BRCA2 genetic testing, and specifically for Christian Arab patients suspected of hereditary BC and/or OC.