ClinVar Genomic variation as it relates to human health

Variant summary: CFHR2 c.79A>G (p.Lys27Glu) results in a conservative amino acid change located in the Sushi/SCR/CCP domain (IPR000436) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0002 in 250268 control chromosomes, predominantly at a frequency of 0.0023 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 15 fold of the estimated maximal expected allele frequency for a pathogenic variant in CFHR2 causing Genetic Atypical Hemolytic Uremic Syndrome phenotype (0.00016), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.79A>G in individuals affected with Genetic Atypical Hemolytic Uremic Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign.

BP4, PP3