Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001041863 | SCV001205509 | pathogenic | Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive | 2019-11-20 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the RAG2 gene (p.Thr98Asnfs*33). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 429 amino acids of the RAG2 protein. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This deletion results in the loss of more than 60% of the protein and affects important functional domains for enzymatic activity and histone interaction (PMID: 16111638, 18033247, 25707801, 26692406). Furthermore, many variants in this region have been reported to be deleterious (PMID: 11133745, 16960852). This variant has not been reported in the literature in individuals with RAG2-related conditions. |