Variant 9-128123014-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025072.7(PTGES2):c.807G>C(p.Lys269Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,614,006 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 53 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 60 hom. )

Consequence

PTGES2
NM_025072.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0760

Variant links:

Genes affected

PTGES2 (HGNC:17822): (prostaglandin E synthase 2) The protein encoded by this gene is a membrane-associated prostaglandin E synthase, which catalyzes the conversion of prostaglandin H2 to prostaglandin E2. This protein also has been shown to activate the transcription regulated by a gamma-interferon-activated transcription element (GATE). Multiple transcript variants have been found for this gene. [provided by RefSeq, Jun 2009]

PTGES2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004923761).

BP6

Variant 9-128123014-C-G is Benign according to our data. Variant chr9-128123014-C-G is described in ClinVar as [Benign]. Clinvar id is 709943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGES2	NM_025072.7 link	c.807G>C	p.Lys269Asn	missense_variant	5/7	ENST00000338961.11	NP_079348.1	Q9H7Z7B3KPZ2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGES2	ENST00000338961.11 link	c.807G>C	p.Lys269Asn	missense_variant	5/7	1	NM_025072.7	ENSP00000345341.6		Q9H7Z7

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2396

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0546

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00408

AC:

1026

AN:

251332

Hom.:

AF XY:

0.00307

AC XY:

417

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0555

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00176

AC:

2568

AN:

1461702

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

1092

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.0588

Gnomad4 AMR exome

AF:

0.00318

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000183

Gnomad4 OTH exome

AF:

0.00368

GnomAD4 genome

AF:

0.0157

AC:

2398

AN:

152304

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1125

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0544

Gnomad4 AMR

AF:

0.00627

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00285

Hom.:

Bravo

AF:

0.0184

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0561

AC:

247

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00514

AC:

624

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.048

T;.;.;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.83

T;.;T;T

MetaRNN

Benign

0.0049

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.64

N;.;.;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.21

N;.;N;N

REVEL

Benign

0.13

Sift

Benign

0.52

T;.;T;T

Sift4G

Benign

0.87

T;T;T;.

Polyphen

0.0020

B;.;.;.

Vest4

0.37

MutPred

0.30

Loss of methylation at K269 (P = 0.0067);.;.;.;

MVP

0.24

MPC

0.25

ClinPred

0.0052

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.070

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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