ClinVar Miner

Submissions for variant NM_000022.4(ADA):c.366_367del (p.Asp123fs)

dbSNP: rs758073965
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001388454 SCV001589452 pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2023-12-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp123Profs*47) 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 (rs758073965, 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: 1074979). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001538803 SCV001756503 pathogenic not provided 2020-05-27 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge
Genome-Nilou Lab RCV001388454 SCV001977517 pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2021-08-10 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001388454 SCV002022165 pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2020-11-19 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003120597 SCV003801182 likely pathogenic Severe combined immunodeficiency disease 2023-01-05 criteria provided, single submitter clinical testing Variant summary: ADA c.366_367delGG (p.Asp123ProfsX47) 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 1.8e-05 in 166232 control chromosomes. To our knowledge, no occurrence of c.366_367delGG in individuals affected with Severe Combined Immunodeficiency and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters (evaluation after 2014) have cited this variant, and all laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics RCV001388454 SCV004211616 likely pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2023-09-04 criteria provided, single submitter clinical testing

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