Calibration of Pathogenicity Due to Variant-Induced Leaky Splicing Defects by Using <i>BRCA2</i> Exon 3 as a Model System.

ABSTRACT: BRCA2 is a clinically actionable gene implicated in breast and ovarian cancer predisposition that has become a high priority target for improving the classification of variants of unknown significance (VUS). Among all BRCA2 VUS, those causing partial/leaky splicing defects are the most challenging to classify because the minimal level of full-length (FL) transcripts required for normal function remains to be established. Here, we explored BRCA2 exon 3 (BRCA2e3) as a model for calibrating variant-induced spliceogenicity and estimating thresholds for BRCA2 haploinsufficiency. In silico predictions, minigene splicing assays, patients' RNA analyses, a mouse embryonic stem cell (mESC) complementation assay and retrieval of patient-related information we

SUBMITTER: Tubeuf H 

PROVIDER: S-EPMC7484206 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature