The intronic BRCA1 c.5407-25T>A variant causing partly skipping of exon 23-a likely pathogenic variant with reduced penetrance?

ABSTRACT: Rare sequence variants in the non-coding part of the BRCA genes are often reported as variants of uncertain significance (VUS), which leave patients and doctors in a challenging position. The aim of this study was to determine the pathogenicity of the BRCA1 c.5407-25T>A variant found in 20 families from Norway, France and United States with suspected hereditary breast and ovarian cancer. This was done by combining clinical and family information with allele frequency data, and assessment of the variant's effect on mRNA splicing. Mean age at breast (n = 12) and ovarian (n = 11) cancer diagnosis in female carriers was 49.9 and 60.4 years, respectively. The mean Manchester score in the 20 families was 16.4. The allele frequency of BRCA1 c.5407-25T>A was 1/64,566 in non-Finnish Europeans (gnom

SUBMITTER: Hoberg-Vetti H 

PROVIDER: S-EPMC7382492 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature