Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
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 |