Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000412743 | SCV000491368 | likely pathogenic | not provided | 2015-12-29 | criteria provided, single submitter | clinical testing | The N173S variant in the RAG2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N173S variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N173S variant is a conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The N173S variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689729 | SCV005186107 | uncertain significance | not specified | 2024-05-01 | criteria provided, single submitter | clinical testing | Variant summary: RAG2 c.518A>G (p.Asn173Ser) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251282 control chromosomes. c.518A>G has been reported in the literature as a compound heterozygous genotype in at-least one individual with combined immunodeficiency and myopathy (example, Henrickson_2018). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence that this variant causes 47.5% V(D)J activity in-vitro (example, Scheutz_2023). The following publications have been ascertained in the context of this evaluation (PMID: 36279417, 30159811). ClinVar contains an entry for this variant (Variation ID: 372841). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Fulgent Genetics, |
RCV005044628 | SCV005683519 | likely pathogenic | Combined immunodeficiency with skin granulomas; Histiocytic medullary reticulosis; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive | 2024-05-03 | criteria provided, single submitter | clinical testing |