Two founder variants account for over 90% of pathogenic BRCA alleles in the Orkney and Shetland Isles in Scotland.

ABSTRACT: For breast and ovarian cancer risk assessment in the isolated populations of the Northern Isles of Orkney and Shetland (in Scotland, UK) and their diasporas, quantifying genetically drifted BRCA1 and BRCA2 pathogenic variants is important. Two actionable variants in these genes have reached much higher frequencies than in cosmopolitan UK populations. Here, we report a BRCA2 splice acceptor variant, c.517-2A>G, found in breast and ovarian cancer families from Shetland. We investigated the frequency and origin of this variant in a population-based research cohort of people of Shetland ancestry, VIKING I. The variant segregates with female breast and ovarian cancer in diagnosed cases and is classified as pathogenic. Exome sequence data from 2108 VIKING I participants with three or more Shetla

SUBMITTER: Kerr SM 

PROVIDER: S-EPMC11607322 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature