ClinVar

Description

Variant summary: FKBP10 c.850G>A (p.Gly284Arg) results in a non-conservative amino acid change located in the FKBP-type peptidyl-prolyl cis-trans isomerase domain (IPR001179) of the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0003 in 1614062 control chromosomes, predominantly at a frequency of 0.0024 within the South Asian subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database (v4.0.0) is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in FKBP10 causing Osteogenesis Imperfecta phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.850G>A in individuals affected with Osteogenesis Imperfecta and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 618130). Based on the evidence outlined above, the variant was classified as likely benign.