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Samples from 824 Caucasian probands were retrospectively collected and the impact of genetic diagnosis and genetic variants epidemiology in this cohort was evaluated. Performance of risk-reducing prophylactic measures, such as prophylactic mastectomy and\/or prophylactic oophorectomy, was assessed through clinical follow-up of patients with a positive genetic result. Pathogenic variants predisposing to HBOC were identified in 11.9% (98\/824) individuals at <jats:italic>BRCA2<\/jats:italic> (47\/98), <jats:italic>BRCA1<\/jats:italic> (24\/98), <jats:italic>PALB2<\/jats:italic> (8\/51), <jats:italic>ATM<\/jats:italic> (7\/51), <jats:italic>CHEK2<\/jats:italic> (6\/51) <jats:italic>MSH6<\/jats:italic>, (2\/51), <jats:italic>RAD51C<\/jats:italic> (2\/51) and <jats:italic>TP53<\/jats:italic> (2\/386). Of them, 11 novel pathogenic variants and 12 VUS were identified, characterized, and submitted to ClinVar. Regarding clinical impact, the risk of developing basal or Her2 breast cancer was increased 15.7 times or 37.5 times for <jats:italic>BRCA1<\/jats:italic> and <jats:italic>MSH6<\/jats:italic> pathogenic variants respectively. On the contrary, the risk of developing basal or luminal A breast cancer was reduced to 81% or 77% for <jats:italic>BRCA2<\/jats:italic> and <jats:italic>BRCA1<\/jats:italic> pathogenic variants, respectively. Finally, 53.2% of individuals testing positive for class IV\/V variants underwent prophylactic surgery (mastectomy, oophorectomy or both) being significantly younger at the cancer diagnosis than those undertaking prophylactic measures (<jats:italic>p<\/jats:italic>\u2009=\u20090.008). Of them, 8 carried a pathogenic\/likely pathogenic variant in other genes different from <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic>, and the remaining (46.7%) decided to continue with clinical follow-up. No differences in pathogenicity or risk of developing cancer were found for <jats:italic>BRCA1\/2<\/jats:italic> between targeted and multigene sequencing strategies; however, NGS was able to resolve a greater proportion of high-risk patients.<\/jats:p>","DOI":"10.1007\/s00438-022-01891-5","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T06:03:10Z","timestamp":1650607390000},"page":"859-871","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of hereditary breast and ovarian cancer germline variants in Granada (Spain): NGS perspective"],"prefix":"10.1007","volume":"297","author":[{"given":"Mar\u00eda","family":"Molina-Zayas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3965-0663","authenticated-orcid":false,"given":"Carmen","family":"Garrido-Navas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Luis","family":"Garc\u00eda-Puche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Barwell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Pedrinaci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margarita Mart\u00ednez","family":"Atienza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Garc\u00eda-Linares","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom\u00e1s","family":"de Haro-Mu\u00f1oz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Antonio","family":"Lorente","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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