Variant rs6472 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000500.9(CYP21A2):c.806G>A(p.Ser269Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,448,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S269T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CYP21A2
NM_000500.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.979

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:

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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;

BP4

Computational evidence support a benign effect (MetaRNN=0.08286491).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CYP21A2	NM_000500.9 linkuse as main transcript	c.806G>A	p.Ser269Asn	missense_variant	7/10	ENST00000644719.2	NP_000491.4
CYP21A2	NM_001128590.4 linkuse as main transcript	c.716G>A	p.Ser239Asn	missense_variant	6/9		NP_001122062.3
CYP21A2	NM_001368143.2 linkuse as main transcript	c.401G>A	p.Ser134Asn	missense_variant	7/10		NP_001355072.1
CYP21A2	NM_001368144.2 linkuse as main transcript	c.401G>A	p.Ser134Asn	missense_variant	6/9		NP_001355073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP21A2	ENST00000644719.2 linkuse as main transcript	c.806G>A	p.Ser269Asn	missense_variant	7/10		NM_000500.9	ENSP00000496625	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000209

AC:

AN:

238976

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

130202

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000151

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1448606

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

720994

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000250

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.24

DANN

Benign

0.81

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.079

M_CAP

Benign

0.064

MetaRNN

Benign

0.083

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.17

N;.;N;.

REVEL

Benign

0.057

Sift

Benign

0.46

T;.;T;.

Sift4G

Benign

0.51

T;.;T;.

Polyphen

0.060

B;B;.;B

Vest4

0.040

MutPred

0.31

Loss of phosphorylation at S269 (P = 0.0384);Loss of phosphorylation at S269 (P = 0.0384);.;Loss of phosphorylation at S269 (P = 0.0384);

MVP

0.64

MPC

0.43

ClinPred

0.036

GERP RS

-3.0

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over