ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.367C>T (p.Arg123Cys)

gnomAD frequency: 0.00016  dbSNP: rs147319483
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000874937 SCV001017184 likely benign Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2024-01-24 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001104352 SCV001261209 uncertain significance Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV001104353 SCV001261210 uncertain significance Histiocytic medullary reticulosis 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Baylor Genetics RCV001331313 SCV001523330 uncertain significance Combined immunodeficiency with skin granulomas 2019-02-06 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genome-Nilou Lab RCV001104352 SCV001652723 uncertain significance Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2021-05-18 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001331313 SCV001806137 uncertain significance Combined immunodeficiency with skin granulomas 2021-07-22 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001104353 SCV001806138 uncertain significance Histiocytic medullary reticulosis 2021-07-22 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224483 SCV003920378 uncertain significance Combined immunodeficiency with skin granulomas; Histiocytic medullary reticulosis; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2023-01-18 criteria provided, single submitter clinical testing This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.03% [21/68030]; https://gnomad.broadinstitute.org/variant/11-36593802-G-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID: 704774). This variant amino acid Cysteine (Cys) is present in several species including multiple mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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