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We identified pathogenic and likely pathogenic (P\/LP) variants of high\u2010and moderate\u2010risk genes using a 23\u2010gene germline cancer panel in 518 patients with hereditary breast and ovarian cancers (HBOC). The frequency of P\/LP variants was 12.4% (64\/518) for high\u2010 and moderate\u2010penetrant genes, namely, <jats:italic>BRCA2<\/jats:italic> (5.6%), <jats:italic>BRCA1<\/jats:italic> (3.3%), <jats:italic>CHEK2<\/jats:italic> (1.2%), <jats:italic>MUTYH<\/jats:italic> (0.8%), <jats:italic>PALB2<\/jats:italic> (0.8%), <jats:italic>MLH1<\/jats:italic> (0.4%), <jats:italic>ATM<\/jats:italic> (0.4%), <jats:italic>BRIP1<\/jats:italic> (0.4%), <jats:italic>TP53<\/jats:italic> (0.2%), and <jats:italic>PMS2<\/jats:italic> (0.2%). Five patients possessed two P\/LP variants in <jats:italic>BRCA1\/2<\/jats:italic> and other genes. We also compared the results from in silico splicing predictive tools and exon splicing patterns from patient samples by analyzing RT\u2010PCR product sequences in six P\/LP intronic variants and two intronic variants of unknown significance (VUS). Altered transcriptional fragments were detected for P\/LP intronic variants in <jats:italic>BRCA1<\/jats:italic>, <jats:italic>BRIP1<\/jats:italic>, <jats:italic>CHEK2<\/jats:italic>, <jats:italic>PARB2<\/jats:italic>, and <jats:italic>PMS2<\/jats:italic>. Notably, we identified an in\u2010frame deletion of the BRCA1 C\u2010terminal (BRCT) domain by exon skipping in <jats:italic>BRCA1<\/jats:italic> c.5152+6T&gt;C\u2014as known VUS\u2014indicating a risk for HBOC. Thus, exon splicing analysis can improve the identification of veiled intronic variants that would aid decision making and determination of hereditary cancer risk.<\/jats:p>","DOI":"10.1111\/cas.14600","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T23:42:33Z","timestamp":1596757353000},"page":"3912-3925","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Exon splicing analysis of intronic variants in multigene cancer panel testing for hereditary breast\/ovarian cancer"],"prefix":"10.1111","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9644-1526","authenticated-orcid":false,"given":"Jin\u2010Sun","family":"Ryu","sequence":"first","affiliation":[{"name":"Division of Translational Science, Research Institute National Cancer Center Goyang 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Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Sung","family":"Kang","sequence":"additional","affiliation":[{"name":"Center for Breast Cancer, Hospital National Cancer Center Goyang Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7576-1512","authenticated-orcid":false,"given":"Seeyoun","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Breast Cancer, Hospital National Cancer Center Goyang Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9009-3508","authenticated-orcid":false,"given":"Dong Ock","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Gynecologic Cancer, Hospital National Cancer Center Goyang Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8964-7158","authenticated-orcid":false,"given":"Myong 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