{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:52:33Z","timestamp":1790628753706,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T00:00:00Z","timestamp":1516147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Genome Research program from Yamanashi Prefecture"},{"name":"Research Grant for Young Scholars"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:p>Utility of combined annotation\u2010dependent depletion (<jats:styled-content style=\"fixed-case\">CADD<\/jats:styled-content>) score was recently reported to rank pathogenicity as C\u2010scores ranging 1\u201099 for both confirmed deleterious mutation. Using C\u2010scores for <jats:italic>BRCA1\/2<\/jats:italic> variants, we tried to constitute the classification system for variant of uncertain significance (<jats:styled-content style=\"fixed-case\">VUS<\/jats:styled-content>), which had been a major problem of genetic testing for hereditary breast and\/or ovarian cancer. We analyzed <jats:italic>BRCA1\/2<\/jats:italic> genes for 283 patients with breast and\/or ovarian cancer. The deleterious mutation and missesne mutations, minor variant, and wild type of <jats:italic>BRCA1<\/jats:italic> and \u2010<jats:italic>2<\/jats:italic> were 5, 27, 251 and 15, 85, 183, respectively. Meanwhile, the variants with C\u2010score \u226510 were involved in 19\/283 (6.7%) in <jats:italic>BRCA1<\/jats:italic> and 34\/283 (12%) in <jats:italic>BRCA2<\/jats:italic>. All deleterious mutations were included in this group. Frequency of personal history and family history of ovarian cancer were significantly high, and frequency of serous adenocarcinoma of ovary and triple negative breast cancer was relatively high in the group with deleterious mutations. Similar findings were seen in patients with variants of C\u2010score \u226510. According to the C\u2010score and population frequency, we could define <jats:styled-content style=\"fixed-case\">VUS<\/jats:styled-content> for 11 patients out of 283 patients (3.9 <jats:styled-content style=\"fixed-case\">CADD<\/jats:styled-content> is useful to classify the variant of <jats:italic>BRCA1\/2<\/jats:italic> and selecting the patient who needs further segregation studies.<\/jats:p>","DOI":"10.1111\/cas.13464","type":"journal-article","created":{"date-parts":[[2017,12,7]],"date-time":"2017-12-07T16:44:05Z","timestamp":1512665045000},"page":"453-461","source":"Crossref","is-referenced-by-count":17,"title":["Combined annotation\u2010dependent depletion score for <i>BRCA1\/2<\/i> variants in patients with breast and\/or ovarian cancer"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0068-4487","authenticated-orcid":false,"given":"Hiroshi","family":"Nakagomi","sequence":"first","affiliation":[{"name":"Department of Breast Surgery Yamanashi Central Hospital Kofu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Mochizuki","sequence":"additional","affiliation":[{"name":"Genome Analysis Center Department of Gynecology Yamanashi Central Hospital Kofu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery Yamanashi Central Hospital Kofu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Hirotsu","sequence":"additional","affiliation":[{"name":"Genome Analysis Center Department of Gynecology Yamanashi Central Hospital Kofu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Amemiya","sequence":"additional","affiliation":[{"name":"Genome Analysis Center Department of Gynecology Yamanashi Central Hospital Kofu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuko","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Gynecology Yamanashi Central Hospital Kofu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Nakagomi","sequence":"additional","affiliation":[{"name":"Graduate School of Interdisciplinary Research University of Yamanashi Kofu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Kubota","sequence":"additional","affiliation":[{"name":"Department of Child Studies Seitoku University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Omata","sequence":"additional","affiliation":[{"name":"Genome Analysis Center Department of Gynecology Yamanashi Central Hospital Kofu Japan"},{"name":"University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgq069"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.144"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1105535"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70228-1"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.6078"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt312"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdv278"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12315"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_7_11_1","unstructured":"Genetic\/Familial High\u2010Risk Assessment: Breast and Ovary. 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