Submissions for variant NM_000500.9(CYP21A2):c.1143G>C (p.Glu381Asp)

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	RCV003234903	SCV003934588	uncertain significance	not specified	2023-05-10	criteria provided, single submitter	clinical testing	Variant summary: CYP21A2 c.1143G>C (p.Glu381Asp) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.4e-06 in 237156 control chromosomes. c.1143G>C has been reported in the literature in individuals affected with Congenital Adrenal Hyperplasia (Kirby-Keyser_1997). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function indicating a 3 fold decrease in enzyme activity (Hsu_1998). The following publications have been ascertained in the context of this evaluation (PMID: 9067760, 10082937). 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. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
OMIM	RCV000012954	SCV000033198	pathogenic	Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency	1997-01-01	no assertion criteria provided	literature only