ClinVar

Description

Variant summary: AGXT c.116_117dupCA (p.Ala40GlnfsX7) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-05 in 247578 control chromosomes (gnomAD). This frequency is not higher than the estimated maximum expected for a pathogenic variant in AGXT causing Primary Hyperoxaluria Type 1 (0.0024), allowing no conclusion about variant significance.c.116_117dupCA has been reported in the literature in individuals affected with Primary Hyperoxaluria Type 1 (Coulter-Mackie_2005, Williams_2007, Williams_2015). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic and one as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.