Splicing Predictions, Splicing Assays, and Variant Classification Using ACMG/AMP Guidelines: Challenges Observed with <i>BRCA1</i> and <i>BRCA2</i> Variants
Following ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel specifications based on ACMG/AMP guidelines, we classified 4 variants as pathogenic or likely pathogenic, 10 as benign or likely benign, and 3 as uncertain significance. This comprehensive analysis of splicing defects refines the clinical classification of BRCA1 and BRCA2 variants and highlights the value of combining experimental and computational evidence to enhance genetic risk assessment in hereditary cancer.
Authors
- Miguel de la Hoya (ORCID: https://orcid.org/0000-0002-8113-1410)
- A. Vega
- Victoria Sampayo
- Miguel E. Aguado‐Barrera (ORCID: https://orcid.org/0000-0002-7822-6726)
- Olivia Fuentes-Ríos (ORCID: https://orcid.org/0000-0002-9089-6765)
- Ana Crujeiras-González (ORCID: https://orcid.org/0000-0003-2266-8231)
- A.M. SÁnchez De Abajo
- Ángel Carracedo
- Carla Coedo-Costa
- Javier Galego-Carro
- Belinda Rodríguez-Lage
- Marta Santamariña
- Ana Blanco-Pérez
Institutions
- Universidade de Santiago de Compostela (ES)
- Hospital Universitario Insular de Gran Canaria (ES)
- Complejo Hospitalario Universitario de Santiago (ES)
- Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (ES)
- Center for Research in Molecular Medicine and Chronic Diseases (ES)
- Fundación Pública Galega de Medicina Xenómica (ES)
- Instituto de Investigación Sanitaria de Santiago (ES)
- Instituto de Investigación de Enfermedades Raras (ES)
Publication Details
- Journal
- Clinical Chemistry
- Published
- 2025-11-26
- DOI
- https://doi.org/10.1093/clinchem/hvaf177
- Primary Topic
- BRCA gene mutations in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00