ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.193G>T (p.Asp65Tyr) (rs909264507)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489480 SCV000577637 pathogenic not provided 2015-08-22 criteria provided, single submitter clinical testing The D65Y missense variant in the RAG2 gene has been reported previously in association withT-negative B-negative severe combine immune deficiency (SCID) (Dalal et al., 2011). It was notobserved in approximately 6,500 individuals of European and African American ancestry in theNHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.D65Y is a non-conservative amino acid substitution, which is likely to impact secondary proteinstructure as these residues differ in polarity, charge, size and/or other properties. This substitutionoccurs at a position that is conserved across species and in silico analysis predicts this variant isprobably damaging to the protein structure/function. In addition, missense variants in nearby residues(R73C/H) have been reported in the Human Gene Mutation Database in association with RAG2-relateddisorders (Stenson et al., 2014), supporting the functional importance of this region of the protein.Please note, the clinical presentation (SCID vs. Omenn syndrome) cannot be predicted from publishedcases because the particular combination of variants and other possible factors can influence diseasepresentation. We interpret D65Y as a pathogenic variant.
Pediatric Immunology Service,The Chaim Sheba Medical Center at Tel HaShomer RCV000681576 SCV000693924 likely pathogenic Severe immunodeficiency, autosomal recessive, T-cell negative, B-cell negative, NK cell-positive; Recombinase activating gene 2 deficiency; Primary immunodeficiency 2018-03-06 criteria provided, single submitter research

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