Variant 6-32038437-CCTG-CCTGCTG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP3BP6

The NM_000500.9(CYP21A2):c.29_31dup(p.Leu10dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CYP21A2
NM_000500.9 inframe_insertion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1O:1

Conservation

PhyloP100: 1.41

Variant links:

Genes affected

CYP21A2 (HGNC:2600): (cytochrome P450 family 21 subfamily A member 2) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for the synthesis of steroid hormones including cortisol and aldosterone. Mutations in this gene cause congenital adrenal hyperplasia. A related pseudogene is located near this gene; gene conversion events involving the functional gene and the pseudogene are thought to account for many cases of steroid 21-hydroxylase deficiency. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CYP21A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_000500.9

BP6

Variant 6-32038437-C-CCTG is Benign according to our data. Variant chr6-32038437-C-CCTG is described in ClinVar as [Benign]. Clinvar id is 12162.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CYP21A2	NM_000500.9 linkuse as main transcript	c.29_31dup	p.Leu10dup	inframe_insertion	1/10	ENST00000644719.2	NP_000491.4
CYP21A2	NM_001128590.4 linkuse as main transcript	c.29_31dup	p.Leu10dup	inframe_insertion	1/9		NP_001122062.3
CYP21A2	NM_001368143.2 linkuse as main transcript	c.-396_-394dup		5_prime_UTR_variant	1/10		NP_001355072.1
CYP21A2	NM_001368144.2 linkuse as main transcript	c.-306_-304dup		5_prime_UTR_variant	1/9		NP_001355073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP21A2	ENST00000644719.2 linkuse as main transcript	c.29_31dup	p.Leu10dup	inframe_insertion	1/10		NM_000500.9	ENSP00000496625	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000128

AC:

AN:

156350

Hom.:

AF XY:

0.0000119

AC XY:

AN XY:

84000

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000851

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000499

AC:

AN:

1402506

Hom.:

Cov.:

AF XY:

0.00000578

AC XY:

AN XY:

692462

show subpopulations

Gnomad4 AFR exome

AF:

0.0000315

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000749

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

21-HYDROXYLASE POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jun 01, 1987

- -

Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Other:1

not provided, no classification provided

literature only

GeneReviews

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over