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. 2025 Sep 16.
doi: 10.1007/s12282-025-01774-8. Online ahead of print.

Prevalence of germline CHEK2 variants in East Asians and Koreans based on population genomic databases

Jong Eun Park  1 , Taeheon Lee  2 , Eun Hye Cho  3 , Mi-Ae Jang  4 , Dongju Won  5 , Boyoung Park  6 , Jung-Sook Ha  7 , Do Hoon Kim  7 , Kyoung-Bo Kim  7 , Chang-Seok Ki  2 , Sun-Young Kong  8   9   10
Affiliations

Prevalence of germline CHEK2 variants in East Asians and Koreans based on population genomic databases

Jong Eun Park et al. Breast Cancer. .

Abstract

Checkpoint kinase 2 (CHEK2) encodes a serine/threonine kinase involved in the DNA damage response through ATM-Chk2-p53 signaling. Its function in maintaining genomic stability classifies it as a tumor suppressor. Heterozygous germline pathogenic variants in CHEK2 are associated with a moderate increase in lifetime risk of breast and prostate cancer. This study assessed the prevalence of CHEK2 variants globally, with a focus on East Asian and Korean populations, for which data have remained limited. We analyzed 125,748 exomes from the Genome Aggregation Database (gnomAD), including 9,197 East Asians, along with additional data from 5,305 individuals in the Korean Variant Archive, 3,617 in Korea4K, and 1,722 in the Korean Reference Genome Database. All CHEK2 variants were classified according to guidelines established by the American College of Medical Genetics, Genomics, and Clinical Genome Resources. The global prevalence of CHEK2 variants was 0.76%, with the highest observed in the Finnish population (2.04%) and the lowest in East Asians (0.11%). By integrating data from Korean genomic databases and gnomAD, representing a total of 12,553 Korean individuals, the overall prevalence in the Korean population was estimated at 0.13%. These findings represent the first integrated estimate of CHEK2 variant frequency in Koreans using multiple population-specific genomic datasets. The results provide a useful reference for future studies and highlight the need for region-specific genetic research to inform counseling and hereditary cancer risk management.

Keywords: CHEK2; East Asian; Korean; Prevalence; gnomAD.

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Conflict of interest statement

Declarations. Conflicts of interest: The authors declare no conflicts of interest. Institutional review board statement: This study was approved by the Institutional Review Board of Hanyang University Guri Hospital (2021-06-29) and was conducted in accordance with the Declaration of Helsinki. Informed consent statement: Not applicable.

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