NM_000500.9(CYP21A2):c.1280G>A (p.Arg427His) AND CYP21A2-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 25, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003390673.4

Allele description [Variation Report for NM_000500.9(CYP21A2):c.1280G>A (p.Arg427His)]

NM_000500.9(CYP21A2):c.1280G>A (p.Arg427His)

Genes:

LOC106780800:CYP21A2 recombination region [Gene]
CYP21A2:cytochrome P450 family 21 subfamily A member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.33

Genomic location:

Preferred name:

NM_000500.9(CYP21A2):c.1280G>A (p.Arg427His)

Other names:

R426H

HGVS:

NC_000006.12:g.32040926G>A
NG_007941.3:g.7622G>A
NG_008337.2:g.73449C>T
NG_045215.1:g.3155G>A
NM_000500.9:c.1280G>AMANE SELECT
NM_001128590.4:c.1190G>A
NM_001368143.2:c.875G>A
NM_001368144.2:c.875G>A
NP_000491.4:p.Arg427His
NP_001122062.3:p.Arg397His
NP_001355072.1:p.Arg292His
NP_001355073.1:p.Arg292His
LRG_829t1:c.1280G>A
LRG_829:g.7622G>A
LRG_829p1:p.Arg427His
NC_000006.11:g.32008703G>A
NM_000500.7:c.1280G>A

Note:

ClinGen staff contributed the HGVS expression for this variant.

Protein change:

R292H; ARG426HIS

Links:

OMIM: 613815.0026; dbSNP: rs151344504

NCBI 1000 Genomes Browser:

rs151344504

Molecular consequence:

NM_000500.9:c.1280G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128590.4:c.1190G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001368143.2:c.875G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001368144.2:c.875G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: CYP21A2-related disorder
Synonyms:: CYP21A2-related condition
Identifiers:

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004118889	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 25, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004118889

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 25, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004118889.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The CYP21A2 c.1280G>A variant is predicted to result in the amino acid substitution p.Arg427His. This variant has been reported to be associated with classic congenital adrenal hyperplasia (CAH) due to significantly decreased enzyme activity (also known as R426H; reported in three sisters with simple virilizing CAH at Baumgartner-Parzer et al. 2001. PubMed ID: 11600539; reported in a salt-wasting CAH patient at Xu et al. 2019. PubMed ID: 30995443). This variant could be a naturally occurring variant in the CYP21A2 gene or a rare deleterious variant originated from the pseudogene CYP21A1P via gene conversion. This variant is interpreted as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine