NM_000500.9(CYP21A2):c.40G>T (p.Ala14Ser) AND Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 11, 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:: RCV001293783.4

Allele description [Variation Report for NM_000500.9(CYP21A2):c.40G>T (p.Ala14Ser)]

NM_000500.9(CYP21A2):c.40G>T (p.Ala14Ser)

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.40G>T (p.Ala14Ser)

HGVS:

NC_000006.12:g.32038462G>T
NG_007941.3:g.5158G>T
NG_045215.1:g.691G>T
NG_055451.1:g.5138G>T
NM_000500.9:c.40G>TMANE SELECT
NM_001128590.4:c.40G>T
NM_001368143.2:c.-385G>T
NM_001368144.2:c.-295G>T
NP_000491.4:p.Ala14Ser
NP_001122062.3:p.Ala14Ser
LRG_829t1:c.40G>T
LRG_829:g.5158G>T
LRG_829p1:p.Ala14Ser
NC_000006.11:g.32006239G>T
NM_000500.7:c.40G>T

Protein change:

A14S

Links:

dbSNP: rs764636694

NCBI 1000 Genomes Browser:

rs764636694

Molecular consequence:

NM_001368143.2:c.-385G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001368144.2:c.-295G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000500.9:c.40G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001128590.4:c.40G>T - missense variant - [Sequence Ontology: SO:0001583]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001482476	Lifecell International Pvt. Ltd	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV002782636	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 11, 2022)	unknown	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

SCV001482476

Lifecell International Pvt. Ltd

no assertion criteria provided

Uncertain significance

germline

clinical testing

SCV002782636

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 11, 2022)

unknown

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
Asian	germline	yes	1	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 Lifecell International Pvt. Ltd, SCV001482476.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Asian	1	not provided	not provided	clinical testing (GTR000592409)	not provided

Description

This variant in exon 1 of the CYP21A2 gene results in the amino acid substitution from Alanine to Serine at codon 14 (p.Ala14Ser) with the sequence change of c.40G>T (NM_000500.7). This variant was observed in a proband with an increased level of 17-OHP enzyme (86.6 nmol/L) which was screened for advanced newborn screening with confirmatory genetic reflex testing at Lifecell Diagnostics. The observed variant is not present in the 1000G database and has a minor allele frequency of 0.0002301 in the gnomAD database. The in-silico predictions by MutationTaster and SIFT are benign and the nucleotide position is not strongly conserved by GERP++.

#	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	(GTR000592409)	1	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002782636.1

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

#	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: Dec 24, 2023

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