ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.685C>T (p.Arg229Trp)

gnomAD frequency: 0.00001  dbSNP: rs765298019
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Pediatric Immunology Service, The Chaim Sheba Medical Center at Tel HaShomer RCV000681587 SCV000693935 uncertain significance Histiocytic medullary reticulosis; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive; Recombinase activating gene 2 deficiency; Inborn error of immunity 2018-03-06 criteria provided, single submitter research
Invitae RCV001042148 SCV001205814 pathogenic Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2023-10-12 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 229 of the RAG2 protein (p.Arg229Trp). This variant is present in population databases (rs765298019, gnomAD 0.002%). This missense change has been observed in individuals with RAG2-related disease (PMID: 11133745, 15025726, 16960852, 28747913). ClinVar contains an entry for this variant (Variation ID: 496624). 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 RAG2 protein function. This variant disrupts the p.Arg229 amino acid residue in RAG2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11133745, 24144642, 26915675). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003471948 SCV004200553 pathogenic Combined immunodeficiency with skin granulomas 2023-04-18 criteria provided, single submitter clinical testing
Natera, Inc. RCV001273255 SCV001456097 pathogenic Histiocytic medullary reticulosis 2020-09-16 no assertion criteria provided clinical testing

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