NM_000500.9(CYP21A2):c.1451_1452delinsC (p.Arg484fs) AND Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Mar 10, 2021
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:: RCV000012941.4

Allele description [Variation Report for NM_000500.9(CYP21A2):c.1451_1452delinsC (p.Arg484fs)]

NM_000500.9(CYP21A2):c.1451_1452delinsC (p.Arg484fs)

Genes:

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

Variant type:

Indel

Cytogenetic location:

6p21.33

Genomic location:

Preferred name:

NM_000500.9(CYP21A2):c.1451_1452delinsC (p.Arg484fs)

Other names:

(p.Arg484ProfsTer58)

HGVS:

NC_000006.12:g.32041097_32041098delinsC
NG_007941.3:g.7793_7794delinsC
NG_008337.2:g.73277_73278delinsG
NG_045215.1:g.3326_3327delinsC
NM_000500.9:c.1451_1452delinsCMANE SELECT
NM_001128590.4:c.1361_1362delinsC
NM_001368143.2:c.1046_1047delinsC
NM_001368144.2:c.1046_1047delinsC
NP_000491.4:p.Arg484fs
NP_001122062.3:p.Arg454fs
NP_001355072.1:p.Arg349fs
NP_001355073.1:p.Arg349fs
LRG_829t1:c.1451_1452delinsC
LRG_829:g.7793_7794delinsC
LRG_829p1:p.Arg484fs
NC_000006.11:g.32008874_32008875delinsC
NM_000500.6:c.1448_1449delinsC

Protein change:

R349fs

Links:

OMIM: 613815.0008; dbSNP: rs397509367

NCBI 1000 Genomes Browser:

rs397509367

Molecular consequence:

NM_000500.9:c.1451_1452delinsC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001128590.4:c.1361_1362delinsC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001368143.2:c.1046_1047delinsC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001368144.2:c.1046_1047delinsC - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Synonyms:: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency; CYP21 deficiency; 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia
Identifiers:: MONDO: MONDO:0008728; MedGen: C2936858; Orphanet: 90794; OMIM: 201910

Recent activity

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zinc finger CCHC domain-containing protein 17 isoform d [Homo sapiens]
zinc finger CCHC domain-containing protein 17 isoform d [Homo sapiens]
gi|543173116|ref|NP_001269498.1|

Protein
Bagre pinnimaculatus isolate 01D4 ATPase 6 (atp6) gene, partial cds; mitochondri...
Bagre pinnimaculatus isolate 01D4 ATPase 6 (atp6) gene, partial cds; mitochondrial
gi|1059520638|gb|KX500659.1|

Nucleotide
maturase K, partial (chloroplast) [Lilium lophophorum var. lophophorum]
maturase K, partial (chloroplast) [Lilium lophophorum var. lophophorum]
gi|378926515|gb|AFC67112.1|

Protein
Leber-like hereditary optic neuropathy, autosomal recessive 2
Leber-like hereditary optic neuropathy, autosomal recessive 2

MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000033183	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 1992)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002496411	Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 10, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23359698, 33552137, 30611409, 29035424, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000033183

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 1992)

germline

literature only

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

SCV002496411

Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 10, 2021)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
Southeast Asian, Indian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Steroid 21-hydroxylase deficiency: three additional mutated alleles and establishment of phenotype-genotype relationships of common mutations.

Wedell A, Ritzén EM, Haglund-Stengler B, Luthman H.

Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7232-6.

PubMed [citation]

PMID:: 1496017
PMCID:: PMC49680

Genotype-phenotype correlation in 1,507 families with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency.

New MI, Abraham M, Gonzalez B, Dumic M, Razzaghy-Azar M, Chitayat D, Sun L, Zaidi M, Wilson RC, Yuen T.

Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2611-6. doi: 10.1073/pnas.1300057110. Epub 2013 Jan 28.

PubMed [citation]

PMID:: 23359698
PMCID:: PMC3574953

See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000033183.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a patient with severe steroid 21-hydroxylase deficiency (201910), Wedell et al. (1992) identified a change of a GG dinucleotide to a C in exon 10, resulting in a frameshift at arginine-484 and a predicted protein with 57 additional amino acids in the C-terminal end.

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

From Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, SCV002496411.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Southeast Asian, Indian	1	not provided	not provided	clinical testing	PubMed (5)

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

Last Updated: Oct 13, 2024

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