2026-04-14T17:00:46Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/732812025-09-24T08:33:48Zcom_10324_1134com_10324_931com_10324_894col_10324_1213

Velázquez Pérez, Carolina Esteban Cardeñosa, Eva Lastra, Enrique Abella, Luis Enrique de la Cruz, Virginia Domínguez Lobatón, María Carmen Duran Dominguez, María Mercedes Infante Sanz, María Del Mar 2019 BRIP1 is a component of the Fanconi Anemia/BRCA pathway responsible for DNA reparation via helicase activity. Some heterozygous variants in BRIP1 could contribute to Hereditary Breast Cancer through a defective DNA repair. The clinical utility of BRIP1 mutations in a familial cancer context is compromised by the conflicting interpretation of “variants of uncertain significance” (VUS). Defining the clinical significance of variants identified in genetic tests is a major challenge; therefore, studies that evaluate the biological effect of these variants are definitely necessary. To contribute to this purpose, we have characterized the variant c.550G>T of BRIP1, a missense mutation with little evidence about its pathogenicity. Since Human Splicing FinderTM predicts the creation of a new exonic splicing enhancer site we decided to perform cDNA analysis revealing that the c.550G>T mutation located in exon 6 led to an aberrant transcript causing exon 5 skipping. Our results demonstrate that the c.550G>T BRIP1 variant disrupts normal splicing, causing exon 5 skipping. Considering that the exon 5 encodes the helicase domain of BRIP1, it is expected an alteration of the function. This finding enhances the interpretation of this VUS, suggesting a potential pathogenic effect. application/pdf https://uvadoc.uva.es/handle/10324/73281 spa Wiley Unraveling the molecular effect of a rare missense mutation in BRIP1 associated with inherited breast cancer info:eu-repo/semantics/article TEXT UVaDOC. Repositorio Documental de la Universidad de Valladolid Hispana