RT info:eu-repo/semantics/article
T1 Characterization of spliceogenic variants located in regions linked to high levels of alternative splicing:BRCA2c.7976+5G > T as a case study
A1 Montalban, Gemma
A1 Fraile-Bethencourt, Eugenia
A1 López-Perolio, Irene
A1 Pérez-Segura, Pedro
A1 Infante Sanz, María Del Mar
A1 Duran Dominguez, María Mercedes
A1 Alonso-Cerezo, María Concepción
A1 López-Fernández, Adrià
A1 Diez, Orland
A1 de la Hoya, Miguel
A1 Velasco, Eladio A.
A1 Gutiérrez-Enríquez, Sara
AB Many BRCA1 and BRCA2 (BRCA1/2) genetic variants have been studied at mRNA level and linked to hereditary breast and ovarian cancer due to splicing alteration. In silico tools are reliable when assessing variants located in consensus splice sites, but we may identify variants in complex genomic contexts for which bioinformatics is not precise enough. In this study, we characterize BRCA2 c.7976 + 5G > T variant located in intron 17 which has an atypical donor site (GC). This variant was identified in three unrelated Spanish families and we have detected exon 17 skipping as the predominant transcript occurring in carriers. We have also detected several isoforms (Δ16‐18, Δ17,18, Δ18, and ▼17q224) at different expression levels among carriers and controls. This study remarks the challenge of interpreting genetic variants when multiple alternative isoforms are present, and that caution must be taken when using in silico tools to identify potential spliceogenic variants located in GC‐AG introns.
PB Wiley-VCH
SN 1059-7794
YR 2018
FD 2018
LK https://uvadoc.uva.es/handle/10324/64447
UL https://uvadoc.uva.es/handle/10324/64447
LA eng
NO Human Mutation 39(9): 1155-1160
DS UVaDOC
RD 14-abr-2025