Submissions for variant NM_001282225.2(ADA2):c.145C>T (p.Arg49Trp)

gnomAD frequency: 0.00013  dbSNP: rs199614299

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000652051	SCV000773918	uncertain significance	Vasculitis due to ADA2 deficiency	2022-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 49 of the ADA2 protein (p.Arg49Trp). This variant is present in population databases (rs199614299, gnomAD 0.05%). This missense change has been observed in individual(s) with Behçet's disease (PMID: 28814775). ClinVar contains an entry for this variant (Variation ID: 375246). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ADA2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV000997858	SCV001153611	uncertain significance	not provided	2019-06-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263670	SCV002543373	uncertain significance	Autoinflammatory syndrome	2016-12-12	criteria provided, single submitter	clinical testing
Department of Immunology, Hospital Universitario Virgen del Rocio	RCV000416313	SCV000493702	pathogenic	Behcet disease	2017-01-13	no assertion criteria provided	case-control