Pathogenic variation distribution of ACMG 3.2 list genes in 11 ethnic groups in southwest China

In recent years, human whole genome sequencing projects in China and abroad have made accidental discoveries in different populations. However, the genetic variants present in the multiethnic population of the southwest region of China remain unclear. The purpose of this study is to elucidate the frequency distribution of different types of genetic variations, particularly pathogenic variants, in ACMG v3.2 list genes among 11 ethnic minority populations from the Guizhou Multi-ethnic Genome Database (GMGD). We collected whole-genome sequencing data from 476 individuals across these 11 GMGD populations and classified the effects of the identified variants according to the ACMG/AMP guideline by GeneBe tools [1]. A total of 521 variants were identified after variant filter, of which 1.5%(8/521) of genetic variants were classified as high confidence pathogenic or potentially pathogenic. The most common P/LP variants were ATP7B : rs762866453, ATP7B : rs191312027 and we observed significant population differences. The three novel variants (ATP7B: rs778732681, PALB2 :rs876660147, GAA: rs765718882) exhibited low to moderate allele frequencies (0.106%–0.42%) in the GMGD population but were undetected in mainstream databases. This study provides information on pathogenic/likely pathogenic variations and their frequencies for 73 disease-related genes across 11 ethnic groups, contributing valuable insights for the advancement of genomic medicine. To the best of our knowledge, this represents the first analysis of clinically incidental genetic variants among these 11 ethnic groups and offers further insights into interethnic genetic differences.