NM_000500.9(CYP21A2):c.1118+2T>C AND Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 23, 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:: RCV001293364.7

Allele description [Variation Report for NM_000500.9(CYP21A2):c.1118+2T>C]

NM_000500.9(CYP21A2):c.1118+2T>C

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.1118+2T>C

HGVS:

NC_000006.12:g.32040586T>C
NG_007941.3:g.7282T>C
NG_008337.2:g.73789A>G
NG_045215.1:g.2815T>C
NM_000500.9:c.1118+2T>CMANE SELECT
NM_001128590.4:c.1028+2T>C
NM_001368143.2:c.713+2T>C
NM_001368144.2:c.713+2T>C
LRG_829t1:c.1118+2T>C
LRG_829:g.7282T>C
NC_000006.11:g.32008363T>C
NM_000500.7:c.1118+2T>C

Links:

dbSNP: rs1776240589

NCBI 1000 Genomes Browser:

rs1776240589

Molecular consequence:

NM_000500.9:c.1118+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001128590.4:c.1028+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001368143.2:c.713+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001368144.2:c.713+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Functional consequence:

sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071]

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
SCV001481973	Lifecell International Pvt. Ltd	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV002061602	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 23, 2021)	germline	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

SCV001481973

Lifecell International Pvt. Ltd

no assertion criteria provided

Pathogenic

germline

clinical testing

SCV002061602

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 23, 2021)

germline

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	germline	yes	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, SCV001481973.2

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

Description

This variant in Intron 8 of the CYP21A2 gene c.1118+2 T>C (NM_000500.7). This variant was observed in a proband with a increased level of 17-OHP enzyme (>296.9 nM/L) which was screened for advanced newborn screening with confirmatory genetic reflex testing at lifecell diagnostics. The reference base is conserved across the species and in-silico predictions by Polyphen and SIFT are damaging. IVS8 + 2 T>C abolishes the intron 8 donor splice, leading to retention of intron 8 with the creation of a premature termination codon.

#	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 Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV002061602.2

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

Description

PVS1, PM2, PM3

#	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		not provided	not provided	not provided	not provided

Last Updated: Jun 10, 2023

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