ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.644C>T (p.Thr215Ile) (rs35691292)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000433357 SCV000514367 benign not specified 2016-12-23 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Pediatric Immunology Service,The Chaim Sheba Medical Center at Tel HaShomer RCV000681585 SCV000693933 uncertain significance Histiocytic medullary reticulosis; Severe combined 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
Invitae RCV001081978 SCV000767448 benign Combined cellular and humoral immune defects with granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2019-12-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000433357 SCV000918149 benign not specified 2018-02-21 criteria provided, single submitter clinical testing Variant summary: RAG2 c.644C>T (p.Thr215Ile) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. However, these predictions have yet to be functionally assessed. The variant allele was found at a frequency of 0.003 in 277112 control chromosomes in the gnomAD database, including 11 homozygotes. The observed variant frequency is approximately 4.22 fold of the estimated maximal expected allele frequency for a pathogenic variant in RAG2 causing Severe Combined Immunodeficiency Syndrome/Omenn Syndrome phenotype (0.00071), strongly suggesting that the variant is benign. The variant, c.644C>T, has been reported in the literature in individuals affected with Severe Combined Immunodeficiency Syndrome/Omenn Syndrome (Tabori_2004, Lev_2012, Meshaal_2015). These reports do not provide unequivocal conclusions about association of the variant with Severe Combined Immunodeficiency Syndrome/Omenn Syndrome. A ClinVar Submission from a clinical diagnostic laboratory (evaluation after 2014) classifies the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Mendelics RCV000645697 SCV001135029 likely benign not provided 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001104047 SCV001260874 benign Histiocytic medullary reticulosis 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001104048 SCV001260875 benign Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
OMIM RCV000014016 SCV000034263 pathogenic Severe combined immunodeficiency, B cell-negative 2004-04-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.