14-52314795-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP4_StrongBP6_Very_StrongBS2

The NM_000956.4(PTGER2):c.247T>G(p.Cys83Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00578 in 1,612,730 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 36 hom. )

Consequence

PTGER2
NM_000956.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.25

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

asthma, nasal polyps, and aspirin intolerance
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

PTGER2 links:

ENSG00000289424 (HGNC:):

ENSG00000289424 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 6: BayesDel_noAF, Cadd, Eigen, FATHMM_MKL, MutationAssessor, PROVEAN [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.016982645).

BP6

Variant 14-52314795-T-G is Benign according to our data. Variant chr14-52314795-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 710814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 792 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGER2	NM_000956.4 link	c.247T>G	p.Cys83Gly	missense_variant	Exon 1 of 2	ENST00000245457.6	NP_000947.2	P43116

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTGER2	ENST00000245457.6 link	c.247T>G	p.Cys83Gly	missense_variant	Exon 1 of 2	1	NM_000956.4	ENSP00000245457.5	P43116
PTGER2	ENST00000557436.2 link	c.-80+294T>G		intron_variant	Intron 1 of 2	3		ENSP00000450933.1	G3V2Y6
ENSG00000289424	ENST00000726802.1 link	n.355+342A>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00521

AC:

793

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00733

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00785

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00550

AC:

1361

AN:

247292

AF XY:

0.00554

show subpopulations

Gnomad AFR exome

AF:

0.000966

Gnomad AMR exome

AF:

0.00643

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.00819

Gnomad OTH exome

AF:

0.00561

GnomAD4 exome

AF:

0.00584

AC:

8527

AN:

1460434

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

4217

AN XY:

726448

show subpopulations

African (AFR)

AF:

0.00105

AC:

AN:

33468

American (AMR)

AF:

0.00673

AC:

301

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

309

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00116

AC:

100

AN:

86238

European-Finnish (FIN)

AF:

0.00124

AC:

AN:

52462

Middle Eastern (MID)

AF:

0.00694

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00656

AC:

7291

AN:

1111602

Other (OTH)

AF:

0.00639

AC:

386

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

583

1165

1748

2330

2913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00520

AC:

792

AN:

152296

Hom.:

Cov.:

AF XY:

0.00530

AC XY:

395

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00139

AC:

AN:

41586

American (AMR)

AF:

0.00732

AC:

112

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00785

AC:

534

AN:

68014

Other (OTH)

AF:

0.0104

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

123

164

205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00663

Hom.:

Bravo

AF:

0.00532

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000688

AC:

ESP6500EA

AF:

0.00872

AC:

ExAC

AF:

0.00530

AC:

641

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0114

EpiControl

AF:

0.00984

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PTGER2: BS2 -

Jun 28, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.59

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.62

MutationAssessor

Pathogenic

3.1

PhyloP100

6.3

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-10

REVEL

Uncertain

0.55

Sift

Uncertain

0.014

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.61

MVP

0.68

MPC

2.0

ClinPred

0.058

GERP RS

4.9

PromoterAI

0.049

Neutral

(source)

Varity_R

0.95

gMVP

0.69

Mutation Taster

=70/30

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

14-52314795-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over