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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Prevalence of pathogenic/likely pathogenic variants in the 24 cancer genes of the ACMG Secondary Findings v2.0 list in a large cancer cohort and ethnicity-matched controls
Genome Medicine, Volume 10, No. 1, Article 607, Year 2018
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Description
Background: Prior research has established that the prevalence of pathogenic/likely pathogenic (P/LP) variants across all of the American College of Medical Genetics (ACMG) Secondary Findings (SF) genes is approximately 0.8-5%. We investigated the prevalence of P/LP variants in the 24 ACMG SF v2.0 cancer genes in a family-based cancer research cohort (n = 1173) and in cancer-free ethnicity-matched controls (n = 982). Methods: We used InterVar to classify variants and subsequently conducted a manual review to further examine variants of unknown significance (VUS). Results: In the 24 genes on the ACMG SF v2.0 list associated with a cancer phenotype, we observed 8 P/LP unique variants (8 individuals; 0.8%) in controls and 11 P/LP unique variants (14 individuals; 1.2%) in cases, a non-significant difference. We reviewed 115 VUS. The median estimated per-variant review time required was 30 min; the first variant within a gene took significantly (p = 0.0009) longer to review (median = 60 min) compared with subsequent variants (median = 30 min). The concordance rate was 83.3% for the variants examined by two reviewers. Conclusion: The 115 VUS required database and literature review, a time- and labor-intensive process hampered by the difficulty in interpreting conflicting P/LP determinations. By rigorously investigating the 24 ACMG SF v2.0 cancer genes, our work establishes a benchmark P/LP variant prevalence rate in a familial cancer cohort and controls. © 2018 The Author(s).
Authors & Co-Authors
Kim, Jung
United States, Bethesda
National Institutes of Health Nih
Luo, Wen
United States, Frederick
National Cancer Institute at Frederick
Wang, Mingyi
United States, Frederick
National Cancer Institute at Frederick
Nickerson, Michael L.
United States, Bethesda
National Institutes of Health Nih
Rotunno, Melissa
United States, Bethesda
National Institutes of Health Nih
Li, Shengchao Alfred
United States, Frederick
National Cancer Institute at Frederick
Dean, Michael C.
United States, Bethesda
National Institutes of Health Nih
de Andrade, Kelvin César
United States, Bethesda
National Institutes of Health Nih
Brazil, Sao Paulo
A.c.camargo Cancer Center
Fortes, Fabiane Silva A.
United States, Bethesda
National Institutes of Health Nih
Brazil, Sao Paulo
A.c.camargo Cancer Center
McMaster, Mary Lou
United States, Bethesda
National Institutes of Health Nih
Alter, Blanche P.
United States, Bethesda
National Institutes of Health Nih
Caporaso, Neil E.
United States, Bethesda
National Institutes of Health Nih
Gadalla, Shahinaz M.
United States, Bethesda
National Institutes of Health Nih
Goldin, Lynn R.
United States, Bethesda
National Institutes of Health Nih
Greene, Mark H.
United States, Bethesda
National Institutes of Health Nih
Loud, Jennifer T.
United States, Bethesda
National Institutes of Health Nih
Freedman, Neal D.
United States, Bethesda
National Institutes of Health Nih
Gapstur, Susan M.
United States, Kennesaw
American Cancer Society
Gaudet, Mia M.
United States, Kennesaw
American Cancer Society
Puig, Susana
Spain, Barcelona
Institut D'investigacions Biomèdiques August pi I Sunyer - Idibaps
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Raras
Hicks, Belynda D.
United States, Frederick
National Cancer Institute at Frederick
Zhu, Bin
United States, Frederick
National Cancer Institute at Frederick
Liu, Jia
United States, Frederick
National Cancer Institute at Frederick
Sampson, Joshua Neil
United States, Bethesda
National Institutes of Health Nih
Chanock, Stephen J.
United States, Bethesda
National Institutes of Health Nih
Mirabello, Lisa J.
United States, Bethesda
National Institutes of Health Nih
Morton, Lindsay Mc Omber
United States, Bethesda
National Institutes of Health Nih
Biesecker, Leslie Glenn
United States, Bethesda
National Institutes of Health Nih
Tucker, Margaret Anne
United States, Bethesda
National Institutes of Health Nih
Savage, Sharon A.
United States, Bethesda
National Institutes of Health Nih
Goldstein, Alisa M.
United States, Bethesda
National Institutes of Health Nih
Stewart, Douglas R.
United States, Bethesda
National Institutes of Health Nih
Statistics
Citations: 14
Authors: 32
Affiliations: 13
Identifiers
Doi:
10.1186/s13073-018-0607-5
ISSN:
1756994X
Research Areas
Cancer
Genetics And Genomics
Study Design
Cross Sectional Study
Cohort Study
Study Approach
Systematic review