{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T16:24:52Z","timestamp":1772814292700,"version":"3.50.1"},"reference-count":68,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001325","name":"Cancer Association of South Africa","doi-asserted-by":"publisher","award":["S007773"],"award-info":[{"award-number":["S007773"]}],"id":[{"id":"10.13039\/501100001325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Concurrent testing of numerous genes for hereditary breast cancer (BC) is available but can result in management difficulties. We evaluated use of an expanded BC gene panel in women of diverse South African ancestries and assessed use of African genomic data to reclassify variants of uncertain significance (VUS). A total of 331 women of White, Black African, or Mixed Ancestry with BC had a 9\u2010gene panel test, with an additional 75 genes tested in those without a pathogenic\/likely pathogenic (P\/LP) variant. The proportion of VUS reclassified using ClinGen gene\u2010specific allele frequency (AF) thresholds or an AF &gt;\u20090.001 in nonguidelines genes in African genomic data was determined. The 9\u2010gene panel identified 58 P\/LP variants, but only two of the P\/LP variants detected using the 75\u2010gene panel were in confirmed BC genes, resulting in a total of 60 (18.1%) in all participants. P\/LP variant prevalence was similar across ancestry groups, but VUS prevalence was higher in Black African and Mixed Ancestry than in White participants. In total, 611 VUS were detected, representing 324 distinct variants. 10.8% (9\/83) of VUS met ClinGen AF thresholds in genomic data while 10.8% (26\/240) in nonguideline genes had an AF &gt;\u20090.001. Overall, 27.0% of VUS occurrences could potentially be reclassified using African genomic data. Thus, expanding the gene panel yielded few clinically actionable variants but many VUS, particularly in participants of Black African and Mixed Ancestry. However, use of African genomic data has the potential to reclassify a significant proportion of VUS.<\/jats:p>","DOI":"10.1002\/gcc.23275","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T10:37:39Z","timestamp":1727347059000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prevalence and Reclassification of Genetic Variants in South African Populations with Breast Cancer"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2966-6327","authenticated-orcid":false,"given":"Tabitha\u00a0S.","family":"Osler","sequence":"first","affiliation":[{"name":"Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences University of the Witwatersrand  Johannesburg South Africa"},{"name":"Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences University of the Witwatersrand  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Health Sciences University of the Witwatersrand  Johannesburg South Africa"},{"name":"Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences University of Stellenbosch and Tygerberg Hospital  Cape Town Parow South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4178-1838","authenticated-orcid":false,"given":"Christopher\u00a0G.","family":"Mathew","sequence":"additional","affiliation":[{"name":"Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences University of the Witwatersrand  Johannesburg South Africa"},{"name":"Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences University of the Witwatersrand  Johannesburg South Africa"},{"name":"Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine King's College London  London 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