Variant chr14-52315339-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000956.4(PTGER2):c.791T>C(p.Ile264Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000397 in 1,612,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

PTGER2
NM_000956.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

Variant links:

Genes affected

PTGER2 (HGNC:9594): (prostaglandin E receptor 2) This gene encodes a receptor for prostaglandin E2, a metabolite of arachidonic acid which has different biologic activities in a wide range of tissues. Mutations in this gene are associated with aspirin-induced susceptibility to asthma. [provided by RefSeq, Oct 2009]

PTGER2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36057907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGER2	NM_000956.4 linkuse as main transcript	c.791T>C	p.Ile264Thr	missense_variant	1/2	ENST00000245457.6	NP_000947.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGER2	ENST00000245457.6 linkuse as main transcript	c.791T>C	p.Ile264Thr	missense_variant	1/2	1	NM_000956.4	ENSP00000245457	P1
PTGER2	ENST00000557436.1 linkuse as main transcript	c.26T>C	p.Ile9Thr	missense_variant	2/3	3		ENSP00000450933

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151396

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

249084

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135004

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000801

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000431

AC:

AN:

1461602

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000558

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151396

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73934

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2024

The c.791T>C (p.I264T) alteration is located in exon 1 (coding exon 1) of the PTGER2 gene. This alteration results from a T to C substitution at nucleotide position 791, causing the isoleucine (I) at amino acid position 264 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;D

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.051

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.5

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-4.1

D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0010

D;T

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.83

.;P

Vest4

0.48

MVP

0.72

MPC

1.6

ClinPred

0.76

GERP RS

4.7

Varity_R

0.56

gMVP

0.62

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over