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Studies predominantly involve hereditary and familial cases, demonstrating a gap in the\u00a0literature regarding\u00a0the identification of germline mutations in unselected patients from Latin-America. Identification of pathogenic\/likely pathogenic (P\/LP) variants is important for shaping national genetic analysis policies, genetic counseling, and early detection strategies. The present study included 400 women with unselected breast cancer (BC), in whom we analyzed ten genes, using Whole Exome Sequencing (WES), know to confer risk for BC, with the aim of determining the genomic profile of previously unreported P\/LP variants in the affected population. Additionally, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to identify Large Genomic Rearrangements (LGRs) in the<jats:italic>BRCA1\/2<\/jats:italic>genes. To ascertain the functional impact of a recurrent intronic variant (<jats:italic>ATM<\/jats:italic>c.5496\u2009+\u20092_5496\u2009+\u20095delTAAG), a minigene assay was conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We ascertained the frequency of P\/LP germline variants in<jats:italic>BRCA2<\/jats:italic>(2.5%)<jats:italic>, ATM<\/jats:italic>(1.25%)<jats:italic>, BRCA1<\/jats:italic>(0.75%),<jats:italic>PALB2<\/jats:italic>(0.50%),<jats:italic>CHEK2<\/jats:italic>(0.50%),<jats:italic>BARD1<\/jats:italic>(0.25%)<jats:italic>,<\/jats:italic>and<jats:italic>RAD51D<\/jats:italic>(0.25%) genes in the population of study. P\/LP variants account for 6% of the total population analyzed. No LGRs were detected in our study. We identified 1.75% of recurrent variants in<jats:italic>BRCA2<\/jats:italic>and<jats:italic>ATM<\/jats:italic>genes. One of them corresponds to the<jats:italic>ATM<\/jats:italic>c.5496\u2009+\u20092_5496\u2009+\u20095delTAAG. Functional validation of this variant demonstrated a splicing alteration probably modifying the\u00a0Pincer domain and subsequent protein structure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study described for the first time the genomic profile of ten risk genes in Colombian women with unselected BC. Our findings underscore the significance of population-based research, advocating the consideration of molecular testing in all women with cancer.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s40246-024-00623-7","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T07:31:33Z","timestamp":1718695893000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Germline mutations of breast cancer susceptibility genes through expanded genetic analysis in unselected Colombian patients"],"prefix":"10.1186","volume":"18","author":[{"given":"Diana Carolina","family":"Sierra-D\u00edaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrien","family":"Morel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora Janeth","family":"Fonseca-Mendoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora Contreras","family":"Bravo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Molano-Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Borras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Munevar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Lema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Idrobo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Trujillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Isabel","family":"Orduz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Lopera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Rojas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Londono-De Los R\u00edos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray","family":"Manneh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Cabrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson","family":"Rubiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jairo","family":"de la Pe\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Catalina","family":"Quintero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Mantilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos M.","family":"Restrepo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"623_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.breast.2022.08.010","volume":"66","author":"M Arnold","year":"2022","unstructured":"Arnold M, Morgan E, Rumgay H, Mafra A, Singh D, Laversanne M, et al. 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