{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T18:08:59Z","timestamp":1761761339663,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Breast and ovarian cancers (BC and OC) are prevalent malignancies in women globally, with germline variants in the BRCA2 gene significantly increasing the risk of developing these cancers. Despite extensive studies, the frequency and impact of BRCA2 variants in women from Jalisco, Mexico, remain underexplored. Objective: The aim of this study was to identify and characterize BRCA2 gene variants in Mexican women diagnosed with BC and OC and to assess their functional and structural consequences using computational analyses. Methodology: Genomic DNA from 140 Mexican women with BC and\/or OC, selected based on clinical criteria suggestive of BRCA2 variants, was sequenced using NGS targeting BRCA2 coding regions. Functional effects were predicted with Ensembl VEP, SIFT, and PolyPhen-2. Structural impacts of missense variants were assessed using HOPE and AlphaFold models. Results: BRCA2 variants were identified in 12.86% of patients, with higher frequency in OC (21.05%) than BC (12%). Several mapped to key functional domains, including BRC repeats and the DNA-binding domain. Many were predicted as deleterious or probably damaging, though clinical classifications were often conflicting. Structural analysis indicated potential disruptions in protein stability or interactions for most missense variants. Clinically, BRCA2-positive BC patients were younger at diagnosis and showed a trend toward lower complete response. Conclusion: BRCA2 variants were found in 12.86% of patients, including six VUSs not reported in other populations. Several affected key functional domains with predicted deleterious effects. Findings support the need for genetic panels tailored to the Mexican population.<\/jats:p>","DOI":"10.3390\/medsci13040248","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:38:22Z","timestamp":1761759502000},"page":"248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and Computational Analysis of BRCA2 Variants in Mexican Women from Jalisco, Mexico, with Breast and Ovarian Cancer"],"prefix":"10.3390","volume":"13","author":[{"given":"Patricia Montserrat","family":"Garc\u00eda-Verd\u00edn","sequence":"first","affiliation":[{"name":"Divisi\u00f3n de Gen\u00e9tica, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"},{"name":"Doctorado en Gen\u00e9tica Humana, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1504-1457","authenticated-orcid":false,"given":"Jos\u00e9 El\u00edas","family":"Garc\u00eda-Ortiz","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Gen\u00e9tica, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9788-1106","authenticated-orcid":false,"given":"Asbiel Felipe","family":"Garibaldi-R\u00edos","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Gen\u00e9tica, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"},{"name":"Doctorado en Gen\u00e9tica Humana, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid Patricia","family":"D\u00e1valos-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Gen\u00e9tica, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra del Carmen","family":"Mendoza-Ruvalcaba","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Gen\u00e9tica, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Teresa","family":"Maga\u00f1a-Torres","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Gen\u00e9tica, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6096-4579","authenticated-orcid":false,"given":"Luis E.","family":"Figuera","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Gen\u00e9tica, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"},{"name":"Doctorado en Gen\u00e9tica Humana, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0387-4996","authenticated-orcid":false,"given":"M\u00f3nica Alejandra","family":"Rosales-Reynoso","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Medicina Molecular, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cesar de Jes\u00fas","family":"Tovar-J\u00e1come","sequence":"additional","affiliation":[{"name":"Doctorado en Gen\u00e9tica Humana, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico"},{"name":"Divisi\u00f3n de Medicina Molecular, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1257-4637","authenticated-orcid":false,"given":"Guillermo Mois\u00e9s","family":"Z\u00fa\u00f1iga-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Medicina Molecular, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2774-6390","authenticated-orcid":false,"given":"Belinda Claudia","family":"G\u00f3mez-Meda","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica Humana \u201cDr. Enrique Corona Rivera\u201d, Departamento de Biolog\u00eda Moleculary Gen\u00f3mica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2233-571X","authenticated-orcid":false,"given":"Blanca Miriam","family":"Torres-Mendoza","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunodeficiencias Humanas y Retrovirus, Divisi\u00f3n de Neurociencias, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"},{"name":"Departamento de Disciplinas Filos\u00f3fico Metodol\u00f3gicas, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Villegas-Pacheco","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dica de Alta Especialidad, Hospital de Gineco-Obstetricia, Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9","family":"G\u00f3mez-Cerda","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dica de Alta Especialidad, Hospital de Gineco-Obstetricia, Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio C\u00e9sar","family":"C\u00e1rdenas Valdez","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dica de Alta Especialidad, Hospital de Gineco-Obstetricia, Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0843-7595","authenticated-orcid":false,"given":"Sergio Osvaldo","family":"Meza-Chavolla","sequence":"additional","affiliation":[{"name":"Unidad de Detecci\u00f3n y Diagn\u00f3stico Cl\u00ednica de Mama, Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4539-1693","authenticated-orcid":false,"given":"Martha Patricia","family":"Gallegos-Arreola","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Gen\u00e9tica, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref_1","first-page":"477","article-title":"Breast Cancer Statistics 2024","volume":"74","author":"Giaquinto","year":"2024","journal-title":"CA Cancer J. 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