VCV000427842.1 - ClinVar

NM_000500.7(CYP21A2):c.[377C>G];[518T>A]

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This genotype includes the following variants

NM_000500.7(CYP21A2):c.[377C>G];[518T>A]

Other names: -
Functional consequence: -
Links: -

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CYP21A2		-	-	GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh37	23	354
LOC106780800	-	-	-	GRCh38 GRCh38	-	304

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency	Pathogenic (1)	criteria provided, single submitter	Sep 16, 2016	RCV000416360.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Sep 16, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (Autosomal recessive inheritance) Affected status: yes Allele origin: inherited	Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital Accession: SCV000485095.2 First in ClinVar: Jan 30, 2017 Last updated: Jan 30, 2017	Age: 0-9 years Sex: female Method: NGS+Sanger sequencing

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
21-Hydroxylase deficiency: Mutational spectrum and Genotype-Phenotype relations analyses by next-generation sequencing and multiplex ligation-dependent probe amplification.	Turan I	European journal of medical genetics	2020	PMID: 31586465
Analysis of phenotypes and genotypes in 84 patients with 21-Hydroxylase deficiency in southern China.	Hou L	Steroids	2019	PMID: 31446012
Genotype-phenotype correlation study and mutational and hormonal analysis in a Chinese cohort with 21-hydroxylase deficiency.	Xu C	Molecular genetics & genomic medicine	2019	PMID: 30968594
Clinical presentation and mutational spectrum in a series of 166 patients with classical 21-hydroxylase deficiency from South China.	Su L	Clinica chimica acta; international journal of clinical chemistry	2018	PMID: 30048636
CYP21A2 mutation update: Comprehensive analysis of databases and published genetic variants.	Simonetti L	Human mutation	2018	PMID: 29035424
21-hydroxylase deficiency-induced congenital adrenal hyperplasia in 230 Chinese patients: Genotype-phenotype correlation and identification of nine novel mutations.	Wang R	Steroids	2016	PMID: 26804566
21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia.	Adam MP	-	2016	PMID: 20301350
High frequency of splice site mutation in 21-hydroxylase deficiency children.	Sharaf S	Journal of endocrinological investigation	2015	PMID: 25501839
Functional studies of novel CYP21A2 mutations detected in Norwegian patients with congenital adrenal hyperplasia.	Brønstad I	Endocrine connections	2014	PMID: 24671123
Functional studies of p.R132C, p.R149C, p.M283V, p.E431K, and a novel c.652-2A>G mutations of the CYP21A2 gene.	Taboas M	PloS one	2014	PMID: 24667412
Structure-phenotype correlations of human CYP21A2 mutations in congenital adrenal hyperplasia.	Haider S	Proceedings of the National Academy of Sciences of the United States of America	2013	PMID: 23359706
Genotype-phenotype correlation in 1,507 families with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency.	New MI	Proceedings of the National Academy of Sciences of the United States of America	2013	PMID: 23359698
Nonclassic 21-hydroxylase deficiency presenting as endometrial hyperplasia with uterine bleeding in a 67-year-old woman.	Vigliani MB	Fertility and sterility	2012	PMID: 22270556
Cardiovascular risk, metabolic profile, and body composition in adult males with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.	Falhammar H	European journal of endocrinology	2011	PMID: 21098686
Classic virilizing congenital adrenal hyperplasia presenting late: case series from Pakistan.	Khan AH	JPMA. The Journal of the Pakistan Medical Association	2009	PMID: 19750867
Gene duplications in 21-hydroxylase deficiency: the importance of accurate molecular diagnosis in carrier detection and prenatal diagnosis.	Ezquieta B	Prenatal diagnosis	2006	PMID: 17042033
An 88-year-old woman diagnosed with adrenal tumor and congenital adrenal hyperplasia: connection or coincidence?	Falhammar H	Journal of endocrinological investigation	2005	PMID: 16075929
Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congenital adrenal hyperplasia.	Dolzan V	European journal of endocrinology	2005	PMID: 15994751
Steroid 21-hydroxylase (P450c21) naturally occurring mutants I172N, V281L and I236n/V237E/M239K exert a dominant negative effect on enzymatic activity when co-expressed with the wild-type protein.	Félix-López X	Journal of pediatric endocrinology & metabolism : JPEM	2003	PMID: 14513879
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency.	White PC	Endocrine reviews	2000	PMID: 10857554
Molecular basis of nonclassical steroid 21-hydroxylase deficiency detected by neonatal mass screening in Japan.	Tajima T	The Journal of clinical endocrinology and metabolism	1997	PMID: 9215318
An intron 1 splice mutation and a nonsense mutation (W23X) in CYP21 causing severe congenital adrenal hyperplasia.	Lajic S	Human genetics	1996	PMID: 8698338
Mutational spectrum of the steroid 21-hydroxylase gene in Sweden: implications for genetic diagnosis and association with disease manifestation.	Wedell A	The Journal of clinical endocrinology and metabolism	1994	PMID: 8175971
A steroid 21-hydroxylase allele concomitantly carrying four disease-causing mutations is not uncommon in the swedish population.	Wedell A	Human genetics	1994	PMID: 8112748
Mutations in steroid 21-hydroxylase (CYP21).	White PC	Human mutation	1994	PMID: 8081391
Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.	Speiser PW	The Journal of clinical investigation	1992	PMID: 1644925
Steroid 21-hydroxylase deficiency: three additional mutated alleles and establishment of phenotype-genotype relationships of common mutations.	Wedell A	Proceedings of the National Academy of Sciences of the United States of America	1992	PMID: 1496017
Substitution of Ile-172 to Asn in the steroid 21-hydroxylase B (P450c21B) gene in a Finnish patient with the simple virilizing form of congenital adrenal hyperplasia.	Partanen J	Human genetics	1991	PMID: 1937474
A missense mutation at Ile172----Asn or Arg356----Trp causes steroid 21-hydroxylase deficiency.	Chiou SH	The Journal of biological chemistry	1990	PMID: 2303461
Determination of functional effects of mutations in the steroid 21-hydroxylase gene (CYP21) using recombinant vaccinia virus.	Tusie-Luna MT	The Journal of biological chemistry	1990	PMID: 2249999
Mutation in the CYP21B gene (Ile-172----Asn) causes steroid 21-hydroxylase deficiency.	Amor M	Proceedings of the National Academy of Sciences of the United States of America	1988	PMID: 3257825
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP21A2	-	-	-	-
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Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_000500.7(CYP21A2):c.[377C>G];[518T>A]

Variant Details

NM_000500.7(CYP21A2):c.[377C>G];[518T>A]

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...