ClinVar

Description

Variant summary: GAA c.2320G>A (p.Asp774Asn) results in a conservative amino acid change in 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 8e-05 in 248994 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than estimated for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) (8e-05 vs 0.0042), allowing no conclusion about variant significance. c.2320G>A has been reported in the literature in at-least one individual affected with late onset features of Glycogen Storage Disease, Type 2 (Pompe Disease) (example, Musumeci_2012). These report(s) do not provide unequivocal conclusions about association of the variant with Glycogen Storage Disease, Type 2 (Pompe Disease). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (VUS, n=4; Likely benign, n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.