ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.1492A>T (p.Lys498Ter)

gnomAD frequency: 0.00002  dbSNP: rs373151027
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001228693 SCV001401105 uncertain significance Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2022-09-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys498*) in the RAG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 30 amino acid(s) of the RAG2 protein. This variant is present in population databases (rs373151027, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RAG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 955968). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
PreventionGenetics, part of Exact Sciences RCV003918788 SCV004729978 likely pathogenic RAG2-related disorder 2023-11-28 criteria provided, single submitter clinical testing The RAG2 c.1492A>T variant is predicted to result in premature protein termination (p.Lys498*). This variant has been reported in the heterozygous state in one individual in a carrier study (Table S9, Reported as genomic position 36570803, Bell et al. 2011. PubMed ID: 21228398). This variant is reported in 0.012% of alleles in individuals of Latino descent in gnomAD. Nonsense variants in RAG2 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Natera, Inc. RCV001833977 SCV002090355 uncertain significance Histiocytic medullary reticulosis 2020-06-02 no assertion criteria provided clinical testing

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