rs9378251

chr6-32038514-C-Achr6-32038514-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2_SupportingPM5PP3_StrongPP5_Moderate

The NM_000500(CYP21A2):c.92C>A(p.Pro31Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P31L) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)

Consequence

CYP21A2
NM_000500 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.34

Links

CYP21A2 (HGNC:2600):

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM2

Very rare variant; Number of alleles below threshold, Median coverage is 32.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr6-32038514-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 12153. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.979

PP5

Variant 6:32038514-C>A is Pathogenic according to our data. Variant chr6-32038514-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 988330. Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CYP21A2	NM_000500.9 linkuse as main transcript	c.92C>A	p.Pro31Gln	missense_variant	1/10	ENST00000644719.2
CYP21A2	NM_001128590.4 linkuse as main transcript	c.92C>A	p.Pro31Gln	missense_variant	1/9
CYP21A2	NM_001368143.2 linkuse as main transcript	c.-333C>A		5_prime_UTR_variant	1/10
CYP21A2	NM_001368144.2 linkuse as main transcript	c.-243C>A		5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP21A2	ENST00000644719.2 linkuse as main transcript	c.92C>A	p.Pro31Gln	missense_variant	1/10		NM_000500.9	P1

Frequencies

GnomAD3 genomes

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Clinical Genetics Karolinska University Hospital, Karolinska University Hospital

Nov 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

Cadd

Uncertain

Dann

Uncertain

0.99

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.79

M_CAP

Pathogenic

0.66

MetaRNN

Pathogenic

0.98

D;D;D;D;D;D

MetaSVM

Uncertain

0.066

MutationTaster

Benign

0.56

D;D

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.4

D;.;D;D;D;.

REVEL

Uncertain

0.58

Sift

Uncertain

0.024

D;.;D;D;D;.

Sift4G

Uncertain

0.0040

D;.;D;D;D;.

Polyphen

1.0

D;D;.;.;.;D

Vest4

0.85

MutPred

0.94

Gain of MoRF binding (P = 0.055);Gain of MoRF binding (P = 0.055);Gain of MoRF binding (P = 0.055);Gain of MoRF binding (P = 0.055);Gain of MoRF binding (P = 0.055);Gain of MoRF binding (P = 0.055);

MVP

0.93

MPC

3.3

ClinPred

0.95

GERP RS

3.6

gMVP

0.73

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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over