NM_000500.9(CYP21A2):c.1451G>A (p.Arg484Gln) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 25, 2015
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000711373.4

Allele description [Variation Report for NM_000500.9(CYP21A2):c.1451G>A (p.Arg484Gln)]

NM_000500.9(CYP21A2):c.1451G>A (p.Arg484Gln)

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.1451G>A (p.Arg484Gln)

HGVS:

NC_000006.12:g.32041097G>A
NG_007941.3:g.7793G>A
NG_008337.2:g.73278C>T
NG_045215.1:g.3326G>A
NM_000500.9:c.1451G>AMANE SELECT
NM_001128590.4:c.1361G>A
NM_001368143.2:c.1046G>A
NM_001368144.2:c.1046G>A
NP_000491.4:p.Arg484Gln
NP_001122062.3:p.Arg454Gln
NP_001355072.1:p.Arg349Gln
NP_001355073.1:p.Arg349Gln
LRG_829t1:c.1451G>A
LRG_829:g.7793G>A
LRG_829p1:p.Arg484Gln
NC_000006.11:g.32008874G>A
NM_000500.7:c.1451G>A

Protein change:

R349Q

Links:

dbSNP: rs200005406

NCBI 1000 Genomes Browser:

rs200005406

Molecular consequence:

NM_000500.9:c.1451G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128590.4:c.1361G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001368143.2:c.1046G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001368144.2:c.1046G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Homo sapiens vacuolar protein sorting 13 homolog B (yeast) (VPS13B), transcript ...
Homo sapiens vacuolar protein sorting 13 homolog B (yeast) (VPS13B), transcript variant 5, mRNA
gi|35493712|ref|NM_017890.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000841736	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Aug 25, 2015)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 12915679, 23359706, 24667412, 24790362, 17119906, 19208730, 26467025
SCV004221766	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Aug 25, 2015)	unknown	clinical testing	PubMed (11) [See all records that cite these PMIDs] 30968594, 32289882, 33864926, 30048636, 12915679, 23359706, 24667412, 24790362, 17119906, 19208730, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000841736

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Aug 25, 2015)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV004221766

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Aug 25, 2015)

unknown

clinical testing

PubMed (11)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genotype-phenotype correlation study and mutational and hormonal analysis in a Chinese cohort with 21-hydroxylase deficiency.

Xu C, Jia W, Cheng X, Ying H, Chen J, Xu J, Guan Q, Zhou X, Zheng D, Li G, Zhao J.

Mol Genet Genomic Med. 2019 Jun;7(6):e671. doi: 10.1002/mgg3.671. Epub 2019 Apr 9.

PubMed [citation]

PMID:: 30968594
PMCID:: PMC6565591

Genetic characterization of a large cohort of Argentine 21-hydroxylase Deficiency.

Fernández CS, Taboas M, Bruque CD, Benavides-Mori B, Belli S, Stivel M, Oneto A, Pasqualini T, Delea M, Espeche LD, Kolomenski JE, Alba L, Buzzalino N, Dain L.

Clin Endocrinol (Oxf). 2020 Jul;93(1):19-27. doi: 10.1111/cen.14190. Epub 2020 May 3.

PubMed [citation]

PMID:: 32289882

See all PubMed Citations (11)

Details of each submission

From Athena Diagnostics, SCV000841736.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

#	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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004221766.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

The CYP21A2 c.1451G>A (p.Arg484Gln) variant (also known as R484Q and R483Q) has been reported in the published literature in several individuals affected with 21 hydroxylase deficiency (PMIDs: 33864926 (2021), 30048636 (2018), 24667412 (2014), 24790362 (2008)) with either a simple virilizing (PMIDs: 32289882 (2020), 17119906 (2007)) or a nonclassic (PMIDs: 30968594 (2019), 19208730 (2009), 12915679 (2003)) phenotype. Functional studies show the variant has severely reduced activity, 1.1-1.89% activity for17-OHP and 2-3.8% activity for progesterone, compared to the wild-type (PMIDs: 24790362 (2008), 17119906 (2007)). The frequency of this variant in the general population, 0.0000088 (2/227246 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, this variant is classified as pathogenic.

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

Last Updated: May 7, 2024

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