Reclassification of Five BRCA1/2 Variants with Unknown Significance Using Complex Functional Study.

ABSTRACT:

Purpose

While BRCA1/2 genes are commonly investigated, variants of unknown significance (VUS) and variants with potential splice effect are still being detected and they represent a substantial challenge in genetic counseling and therapy.

Materials and methods

Out of genetically tested 3,568 hereditary breast and ovarian cancer probands five, functionally not investigated variants with potential splice-modifying effect were subjected to functional characterization. Transcript-level analysis on peripheral blood-derived RNA of the carriers was performed to test aberrant splicing. The completeness of the aberrant splicing event was also studied, existence and extent of nonsense-mediated decay was even addressed. Clinical and phenotype data, pedigree and co-segregation analyses

SUBMITTER: Bozsik A 

PROVIDER: S-EPMC9582465 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature