ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.115A>G (p.Arg39Gly)

dbSNP: rs121917897
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen RCV003991458 SCV004809139 pathogenic Recombinase activating gene 2 deficiency 2024-02-26 reviewed by expert panel curation NM_000536.4(RAG2):c.115A>G is a missense variant predicted to cause substitution of Arginine by Glycine at amino acid 39 (p.Arg39Gly).This missense variant is located in the core domain (amino acids 1-383) (PM1_supporting).The variant is absent in gnomAD v4 (PM2_supporting). Patient with SCID (0.5 pt.), genome sequencing conducted (0.5 pt.),T-B-NK+ lymphocyte subset profile (0.5 pt.) :Total :1.5 pts. PP4 met (PMID: 11313270). This variant was found to segregate in 2 affected siblings from one family (PP1_moderate) (PMID: 11313270).Two patients (PMID: 11313270) were found compound heterozygous for R39G and R229Q (pathogenic variant) ;total : 2pts. (PM3_strong).This variant showed <25 % of wild type activity in In vitro V(D)J recombination assay (PS3_moderate) (PMID: 11313270). In summary, this variant meets the criteria to be classified as a Pathogenic variant for autosomal recessive severe combined immunodeficiency due to RAG2 deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PM1_supporting,PM2_supporting,PP4 met,PP1_moderate,PM3_strong,PS3_moderate(VCEP specifications version 1).
Pediatric Immunology Service, The Chaim Sheba Medical Center at Tel HaShomer RCV000681573 SCV000693921 likely pathogenic 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
OMIM RCV000014017 SCV000034264 pathogenic Severe combined immunodeficiency, B cell-negative 2001-05-01 no assertion criteria provided literature only
OMIM RCV000014018 SCV000034265 pathogenic Histiocytic medullary reticulosis 2001-05-01 no assertion criteria provided literature only

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