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Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals


Clarifying allele frequencies of disease-related genetic variants in a population is important in genomic medicine; however, such data is not yet available for the Japanese population. To estimate frequencies of actionable pathogenic variants in the Japanese population, we examined the reported pathological variants in genes recommended by the American College of Medical Genetics and Genomics (ACMG) in our reference panel of genomic variations, 2KJPN, which was created by whole-genome sequencing of 2049 individuals of the resident cohort of the Tohoku Medical Megabank Project. We searched for pathogenic variants in 2KJPN for 57 autosomal ACMG-recommended genes responsible for 26 diseases and then examined their frequencies. By referring to public databases of pathogenic variations, we identified 143 reported pathogenic variants in 2KJPN for the 57 ACMG recommended genes based on a classification system. At the individual level, 21% of the individuals were found to have at least one reported pathogenic allele. We then conducted a literature survey to review the variants and to check for evidence of pathogenicity. Our results suggest that a substantial number of people have reported pathogenic alleles for the ACMG genes, and reviewing variants is indispensable for constructing the information infrastructure of genomic medicine for the Japanese population.

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This work was supported by Tohoku Medical Megabank Project from MEXT and Japan Agency for Medical Research and Development (AMED), and by the grant “Advanced Genome Research and Bioinformatics Study to Facilitate Medical Innovation”, also by AMED. This research was also supported by the Center of Innovation Program from Japan Science and Technology Agency, JST. All computational resources were provided by the ToMMo supercomputer system. We are indebted to all volunteers who participated in this Tohoku Medical Megabank project. We would like to acknowledge all the members associated with this project; the member list is available at the following web site: We would like to thank Editage ( for English language editing.

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The authors declare that they have no competing interests.

Correspondence to Yumi Yamaguchi-Kabata or Kengo Kinoshita.

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