Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV001263784 | SCV005375392 | likely pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2024-05-28 | reviewed by expert panel | curation | The c.516C>A (p.Tyr172Ter) (NM_000022.4) variant in ADA is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 6/12 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1_Met). The filtering allele frequency (the upper threshold of the 95% CI of 5/86250) of the c.516C>A variant in ADA is 0.00002194 for South Asian chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.0001742) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting).There are no publications for this variant in the literature. As per the SCID VCEP specifications and the Bayesian interpretation of the ACMG/AMP combining rules, 1 very strong and 1 supporting criteria results in a Likely Pathogenic classification. In summary, this variant meets the criteria to be classified as a Likely Pathogenic variant for autosomal recessive severe combined immunodeficiency due to ADA deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PVS1, PM2_supporting. |
| Myriad Genetics, |
RCV001263784 | SCV001441877 | likely pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2019-06-15 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001263784 | SCV004213434 | likely pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2023-05-01 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV001263784 | SCV004238416 | likely pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2023-05-16 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001263784 | SCV004492394 | pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr172*) in the ADA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADA are known to be pathogenic (PMID: 26255240, 26376800). This variant is present in population databases (rs748810619, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ADA-related conditions. ClinVar contains an entry for this variant (Variation ID: 983781). For these reasons, this variant has been classified as Pathogenic. |