Submissions for variant NM_000500.9(CYP21A2):c.92C>T (p.Pro31Leu) (rs9378251)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics Inc	RCV000711390	SCV000841753	pathogenic	not provided	2021-04-20	criteria provided, single submitter	clinical testing	Frequency data for this variant in the general population cannot be distinguished from that of the CYP21P pseudogene, and are therefore uninformative in assessment of variant pathogenicity. In some published literature, this variant is referred to as Pro30Leu or *8. In multiple individuals, this variant has been seen in trans with other recessive pathogenic variants in CYP21A2, suggesting this variant is also pathogenic. This variant has been reported to associate with non-classic congenital adrenal hyperplasia (CAH). Assessment of experimental evidence suggests this variant results in abnormal protein function. Studies have shown this variant significantly reduces enzymatic activity (PMID: 20080860, 23927611, 24953648, 28539365).
Fulgent Genetics,Fulgent Genetics	RCV000012938	SCV000893710	pathogenic	Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency	2018-10-31	criteria provided, single submitter	clinical testing
Myriad Women's Health, Inc.	RCV000012938	SCV001194148	pathogenic	Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency	2019-12-17	criteria provided, single submitter	clinical testing	NM_000500.7(CYP21A2):c.92C>T(P31L) is classified as pathogenic in the context of congenital adrenal hyperplasia, CYP21A2-related and is associated with the non-classic form of disease. Sources cited for classification include the following: PMID 23142378, 16427797, 23359698, 1644925, 2072928 and 9215318. Classification of NM_000500.7(CYP21A2):c.92C>T(P31L) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital	RCV000711390	SCV001449882	pathogenic	not provided	2017-02-08	criteria provided, single submitter	clinical testing
OMIM	RCV000012938	SCV000033179	pathogenic	Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency	1997-07-01	no assertion criteria provided	literature only
GeneReviews	RCV000012938	SCV000086805	pathologic	Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency	2013-08-29	no assertion criteria provided	curation	Converted during submission to Pathogenic.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV000012938	SCV000590901	pathogenic	Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency	2017-07-28	no assertion criteria provided	clinical testing	This variant has been reported in 1000 genomes database, dbSNP(rs9378251) and HGMD. The in silico prediction of this variant is disease-causing by MutationTaster.