ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.859del (p.Cys287fs)

gnomAD frequency: 0.00001  dbSNP: rs754975137
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001999973 SCV002228994 pathogenic Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2023-11-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys287Alafs*6) in the RAG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 241 amino acid(s) of the RAG2 protein. This variant is present in population databases (rs754975137, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with severe combined immunodeficiency/ Omenn syndrome (PMID: 24144642; Invitae). ClinVar contains an entry for this variant (Variation ID: 1452768). This variant disrupts the p.Trp453 amino acid residue in RAG2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10891502, 12200379, 20234091). 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 RCV004571712 SCV005054064 pathogenic Combined immunodeficiency with skin granulomas 2024-03-07 criteria provided, single submitter clinical testing

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