ClinVar Miner

Submissions for variant NM_000022.4(ADA):c.221G>T (p.Gly74Val)

gnomAD frequency: 0.00009  dbSNP: rs199422328
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000002054 SCV000953974 pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 74 of the ADA protein (p.Gly74Val). This variant is present in population databases (rs199422328, gnomAD 0.03%). This missense change has been observed in individual(s) with adenosine deaminase deficiency (PMID: 8614422, 27129325; Invitae). ClinVar contains an entry for this variant (Variation ID: 1977). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects ADA function (PMID: 8614422, 9758612). This variant disrupts the p.Gly74 amino acid residue in ADA. Other variant(s) that disrupt this residue have been observed in individuals with ADA-related conditions (PMID: 30290665), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000002054 SCV004213378 pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2023-06-20 criteria provided, single submitter clinical testing
OMIM RCV000002054 SCV000022212 pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 1996-05-23 no assertion criteria provided literature only
Natera, Inc. RCV000002054 SCV002095334 likely pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2020-08-12 no assertion criteria provided clinical testing

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