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NM_000500.9(CYP21A2):c.1226G>T (p.Arg409Leu) AND CYP21A2-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 13, 2023
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV003901722.2

Allele description [Variation Report for NM_000500.9(CYP21A2):c.1226G>T (p.Arg409Leu)]

NM_000500.9(CYP21A2):c.1226G>T (p.Arg409Leu)

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.1226G>T (p.Arg409Leu)
HGVS:
  • NC_000006.12:g.32040872G>T
  • NG_007941.3:g.7568G>T
  • NG_008337.2:g.73503C>A
  • NG_045215.1:g.3101G>T
  • NM_000500.9:c.1226G>TMANE SELECT
  • NM_001128590.4:c.1136G>T
  • NM_001368143.2:c.821G>T
  • NM_001368144.2:c.821G>T
  • NP_000491.4:p.Arg409Leu
  • NP_001122062.3:p.Arg379Leu
  • NP_001355072.1:p.Arg274Leu
  • NP_001355073.1:p.Arg274Leu
  • LRG_829t1:c.1226G>T
  • LRG_829:g.7568G>T
  • LRG_829p1:p.Arg409Leu
  • NC_000006.11:g.32008649G>T
  • NM_000500.7:c.1226G>T
Protein change:
R274L
Molecular consequence:
  • NM_000500.9:c.1226G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128590.4:c.1136G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368143.2:c.821G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368144.2:c.821G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004717568PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(Dec 13, 2023) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004717568.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The CYP21A2 c.1226G>T variant is predicted to result in the amino acid substitution p.Arg409Leu. This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant falls within a highly paralogous region. Allele frequency data should be interpreted with caution. Likely not originated from the pseudogene CYP21A1P, this rare variant has been reported to be associated with salt-wasting (SW) congenital adrenal hyperplasia (CAH) likely due to the extensive loss of hydrogen bonds and then destabilized structural elements of the enzyme (also known as R408L; Yu et al. 2011. PubMed ID: 21198393; Haider et al. 2013. PubMed ID: 23359706). Of note, other substitutions at the same codon have been reported to be pathogenic for CAH (see for example, Haider et al. 2013. PubMed ID: 23359706). This variant is interpreted as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024