Submissions for variant NM_000536.4(RAG2):c.1295C>T (p.Pro432Leu)

dbSNP: rs753677011

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001779459	SCV002014868	uncertain significance	not specified	2021-10-11	criteria provided, single submitter	clinical testing	Variant summary: RAG2 c.1295C>T (p.Pro432Leu) results in a non-conservative amino acid change located in the Recombination activating protein 2, PHD domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251454 control chromosomes. c.1295C>T has been reported in the literature in two individuals affected with Severe Combined Immunodeficiency Syndrome in the compound heterozygous state (Bai_2016, Hu_2017). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Baylor Genetics	RCV003475084	SCV004200546	likely pathogenic	Combined immunodeficiency with skin granulomas	2024-03-26	criteria provided, single submitter	clinical testing