ClinVar Miner

Submissions for variant NM_001282225.2(ADA2):c.1358A>G (p.Tyr453Cys)

gnomAD frequency: 0.00007  dbSNP: rs376785840
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000106380 SCV000818918 pathogenic Vasculitis due to ADA2 deficiency 2023-08-04 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 453 of the ADA2 protein (p.Tyr453Cys). This variant is present in population databases (rs376785840, gnomAD 0.01%). This missense change has been observed in individual(s) with ADA2 deficiency and auto-inflammatory disease in multiple families (PMID: 24552284, 27252897). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 120299). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. For these reasons, this variant has been classified as Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002262702 SCV002543366 likely pathogenic Autoinflammatory syndrome 2020-01-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002477260 SCV002792488 pathogenic Sneddon syndrome; Vasculitis due to ADA2 deficiency 2021-12-15 criteria provided, single submitter clinical testing
OMIM RCV000106380 SCV000143884 pathogenic Vasculitis due to ADA2 deficiency 2014-03-06 no assertion criteria provided literature only
GeneReviews RCV000106380 SCV000994594 not provided Vasculitis due to ADA2 deficiency no assertion provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.