Dataset Information

Frequency and spectrum of actionable pathogenic secondary findings in Taiwanese exomes.

ABSTRACT: BACKGROUND:Exome sequencing has recently become more readily available, and more information about incidental findings has been disclosed. However, data from East Asia are scarce. We studied the application of exome sequencing to the identification of pathogenic/likely pathogenic variants in the ACMG 59 gene list and the frequency of these variants in the Taiwanese population. METHODS:This study screened 161 Taiwanese exomes for variants from the ACMG 59 gene list. The identified variants were reviewed based on information from different databases and the available literature and classified according to the ACMG standard guidelines. RESULTS:We identified seven pathogenic/likely pathogenic variants in eight individuals, with five participants with autosomal recessive variants in one allele and three participants with autosomal dominant variants. Approximately 1.86% (3/161) of the Taiwanese individuals had a reportable pathogenic/likely pathogenic variant as determined by whole-exome sequencing (WES), which was comparable to the proportions published previously in other countries. We further investigated the high carrier rate of rare variants in the ATP7B gene, which might indicate a founder effect in our population. CONCLUSION:This study was the first to provide Taiwanese population data of incidental findings and emphasized a high carrier rate of candidate pathogenic/likely pathogenic variants in the ATP7B gene.

SUBMITTER: Kuo CW

PROVIDER: S-EPMC7549563 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Frequency and spectrum of actionable pathogenic secondary findings in Taiwanese exomes.

Kuo Chieh-Wen CW Hwu Wuh-Liang WL Chien Yin-Hsiu YH Hsu Ching C Hung Miao-Zi MZ Lin I-Lin IL Lai Feipei F Lee Ni-Chung NC

Molecular genetics & genomic medicine 20200814 10

<h4>Background</h4>Exome sequencing has recently become more readily available, and more information about incidental findings has been disclosed. However, data from East Asia are scarce. We studied the application of exome sequencing to the identification of pathogenic/likely pathogenic variants in the ACMG 59 gene list and the frequency of these variants in the Taiwanese population.<h4>Methods</h4>This study screened 161 Taiwanese exomes for variants from the ACMG 59 gene list. The identified ...[more]

PMID: 32794656

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Project description:The American College of Medical Genetics and Genomics (ACMG) recommends that clinical sequencing laboratories return secondary findings in 56 genes associated with medically actionable conditions. Our goal was to apply a systematic, stringent approach consistent with clinical standards to estimate the prevalence of pathogenic variants associated with such conditions using a diverse sequencing reference sample. Candidate variants in the 56 ACMG genes were selected from Phase 1 of the 1000 Genomes dataset, which contains sequencing information on 1,092 unrelated individuals from across the world. These variants were filtered using the Human Gene Mutation Database (HGMD) Professional version and defined parameters, appraised through literature review, and examined by a clinical laboratory specialist and expert physician. Over 70,000 genetic variants were extracted from the 56 genes, and filtering identified 237 variants annotated as disease causing by HGMD Professional. Literature review and expert evaluation determined that 7 of these variants were pathogenic or likely pathogenic. Furthermore, 5 additional truncating variants not listed as disease causing in HGMD Professional were identified as likely pathogenic. These 12 secondary findings are associated with diseases that could inform medical follow-up, including cancer predisposition syndromes, cardiac conditions, and familial hypercholesterolemia. The majority of the identified medically actionable findings were in individuals from the European (5/379) and Americas (4/181) ancestry groups, with fewer findings in Asian (2/286) and African (1/246) ancestry groups. Our results suggest that medically relevant secondary findings can be identified in approximately 1% (12/1092) of individuals in a diverse reference sample. As clinical sequencing laboratories continue to implement the ACMG recommendations, our results highlight that at least a small number of potentially important secondary findings can be selected for return. Our results also confirm that understudied populations will not reap proportionate benefits of genomic medicine, highlighting the need for continued research efforts on genetic diseases in these populations.

Dataset Information

Frequency and spectrum of actionable pathogenic secondary findings in Taiwanese exomes.

Publications

Frequency and spectrum of actionable pathogenic secondary findings in Taiwanese exomes.

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