Submissions for variant NM_000536.4(RAG2):c.954del (p.Phe318fs)

dbSNP: rs2133312873

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001379080	SCV001576813	likely pathogenic	Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive	2020-03-05	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the C-terminus of the RAG2 protein. Other variant(s) that disrupt this region (p.His468Argfs*16, p.E480*, p.Arg523Glufs*49) have been observed in individuals with RAG2-related conditions (PMID:26915675, 21624848, 24144642 ). This suggests that this may be a clinically significant region of the protein. This variant has not been reported in the literature in individuals with RAG2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the RAG2 gene (p.Phe318Leufs*31). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 210 amino acids of the RAG2 protein.