ClinVar

Description

Variant summary: ATP13A2 c.2348G>A (p.Arg783Gln) results in a conservative amino acid change located in the P-type ATPase, haloacid dehalogenase domain (IPR044492) 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 0.00037 in 282148 control chromosomes, predominantly at a frequency of 0.0038 within the African or African-American subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 20 fold of the estimated maximal expected allele frequency for a pathogenic variant in ATP13A2 causing Neurodegeneration With Brain Iron Accumulation phenotype (0.00019), 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.2348G>A in individuals affected with Neurodegeneration With Brain Iron Accumulation and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 465258). Based on the evidence outlined above, the variant was classified as likely benign.