ClinVar Miner

Submissions for variant NM_000022.4(ADA):c.603C>G (p.Tyr201Ter)

dbSNP: rs1555844395
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen RCV000670951 SCV004242243 pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2024-01-24 reviewed by expert panel curation The c.603C>G (p.Tyr201Ter) (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 highest population minor allele frequency in gnomAD v4 is 0.00002992 (1/33422 alleles) in African/African American population, 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. Patient # 46 was found to be heterozygous for c.603C>G (p.Tyr201*) and c.632G>A (p.Arg211His) which is classified as pathogenic for SCID by the ClinGen SCID VCEP (1 pt.) (PMID: 26255240, PM3). In summary, this variant meets the criteria to be classified as a 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: PM2_supporting,PM3,PVS1 (VCEP specifications version 1).
Counsyl RCV000670951 SCV000795876 likely pathogenic Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2017-11-21 criteria provided, single submitter clinical testing

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