2026-05-05T18:34:50Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/644472024-12-16T10:44:49Zcom_10324_1134com_10324_931com_10324_894col_10324_1213

Characterization of spliceogenic variants located in regions linked to high levels of alternative splicing:BRCA2c.7976+5G > T as a case study Montalban, Gemma Fraile-Bethencourt, Eugenia López-Perolio, Irene Pérez-Segura, Pedro Infante Sanz, María Del Mar Duran Dominguez, María Mercedes Alonso-Cerezo, María Concepción López-Fernández, Adrià Diez, Orland de la Hoya, Miguel Velasco, Eladio A. Gutiérrez-Enríquez, Sara 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. 2024-01-11T11:49:51Z 2024-01-11T11:49:51Z 2024-01-11T11:49:51Z 2018 info:eu-repo/semantics/article Human Mutation 39(9): 1155-1160 1059-7794 https://uvadoc.uva.es/handle/10324/64447 10.1002/humu.23583 1155 9 1160 Human Mutation 39 eng https://doi.org/10.1002/humu.23583 info:eu-repo/semantics/openAccess Wiley-VCH