Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001484684 | SCV001689105 | likely benign | Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive | 2024-11-23 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001806203 | SCV002051168 | likely benign | not specified | 2021-12-16 | criteria provided, single submitter | clinical testing | Variant summary: RAG1 c.575G>A (p.Cys192Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00017 in 250944 control chromosomes, predominantly at a frequency of 0.0022 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1.39 fold of the estimated maximal expected allele frequency for a pathogenic variant in RAG1 causing Severe Combined Immunodeficiency phenotype (0.0016), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.575G>A has been reported in the literature in individuals affected with Omenn Syndrome (Sobacchi_2006). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |