Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Rady Children's Institute for Genomic Medicine, |
RCV003335900 | SCV004046174 | likely pathogenic | Neurodevelopmental disorder with language impairment and behavioral abnormalities | criteria provided, single submitter | clinical testing | A different amino acid change at the same residue (p.Ala639Ser) has been previously reported in two patients with intellectual disability and neurodevelopmental abnormalities (PMID: 31300657). The GRIA2 gene is constrained against variation (Z-score= 4.56 and pLI = 1), and missense variants are a common mechanism of disease (HGMD, ClinVar database; PMID: 31300657). The c.1916C>G (p.Ala639Gly) variant is absent from the gnomAD population database and thus is presumed to be rare. The c.1916C>G (p.Ala639Gly) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a discordant effect on protein function. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.1916C>G (p.Ala639Gly) variant is classified as Likely Pathogenic. |