ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.1433G>A (p.Cys478Tyr)

gnomAD frequency: 0.00001  dbSNP: rs121918573
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Total submissions: 5
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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 RCV000681602 SCV000693950 uncertain significance 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
Baylor Genetics RCV003460470 SCV004206067 likely pathogenic Combined immunodeficiency with skin granulomas 2023-02-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003764566 SCV004570817 pathogenic Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2023-10-18 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 478 of the RAG2 protein (p.Cys478Tyr). This variant is present in population databases (rs121918573, gnomAD 0.007%). This missense change has been observed in individuals with severe combined immunodeficiency (PMID: 8810255, 11133745). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13129). 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. Experimental studies have shown that this missense change affects RAG2 function (PMID: 8810255, 20234091, 26692406, 29772310, 31388879). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005049335 SCV005683499 likely pathogenic Combined immunodeficiency with skin granulomas; Histiocytic medullary reticulosis; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2024-03-06 criteria provided, single submitter clinical testing
OMIM RCV000014009 SCV000034256 pathogenic Severe combined immunodeficiency, B cell-negative 1996-10-04 no assertion criteria provided literature only

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