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Actionable secondary findings in the 73 ACMG-recommended genes in 1559 Thai exomes

Abstract

High-throughput DNA sequencing provides not only primary diagnosis but also makes available other genetic variants with potential health implications. the American College of Medical Genetics and Genomics (ACMG) has recommended a list of medically actionable genes since 2013 and very recently released an updated ACMG SF v3.0 list comprising 73 genes. Here, we analyzed exome data of 1559 unrelated Thai individuals to determine the frequency and spectrum of pathogenic (P) or likely pathogenic (LP) variants in the 73 genes. Based on the ACMG guidelines for the interpretation of sequence variants, 68 different P/LP variants in 26 genes associated with 18 diseases inherited in an autosomal-dominant manner of 186 individuals (11.9%; 186/1559) were identified. Of these, 22 P/LP variants in 15 genes associated with 13 diseases of 85 individuals (5.5%; 85/1559) were also reported as P/LP in the ClinVar archive. The majority harbored variants in genes related to cardiovascular diseases (4.7%; 74/1559), followed by cancer phenotypes (0.5%; 8/1559). None of the individuals in our cohort harbored biallelic variants in genes responsible for diseases inherited in an autosomal recessive manner. The results would serve as a basis for precision medicine practice at individual and population levels.

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Acknowledgements

We would like to thank the patients and their families for participating in this study, clinicians for collecting clinical information, and bioinformaticians for analyzing and managing the database. This work was supported by Thailand Research Fund (DPG6180001), Health Systems Research Institute, TSRI Fund (CU_FRB640001_01_30_10), and the Second Century Fund (C2F), and Ratchadaphiseksomphot Endowment Fund of Chulalongkorn University (764002-HE01).

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W.C.: data curation, formal analysis, and writing the original draft; V.S.: conceptualization, funding acquisition, and editing the manuscript.

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Correspondence to Vorasuk Shotelersuk.

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Chetruengchai, W., Shotelersuk, V. Actionable secondary findings in the 73 ACMG-recommended genes in 1559 Thai exomes. J Hum Genet 67, 137–142 (2022). https://doi.org/10.1038/s10038-021-00982-2

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