Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genome Diagnostics Laboratory, |
RCV002264610 | SCV002543402 | uncertain significance | Autoinflammatory syndrome | 2021-09-13 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003746611 | SCV004539580 | likely pathogenic | Vasculitis due to ADA2 deficiency | 2023-01-12 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects ADA2 function (PMID: 31945408). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ADA2 protein function. ClinVar contains an entry for this variant (Variation ID: 1694264). This missense change has been observed in individuals with DADA2 deficiency and/or primary immunodeficiency (PMID: 29564582, 31945408, 32888943). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 321 of the ADA2 protein (p.Gly321Glu). |