9-128122474-C-T

Position:

• chr9-128122474-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025072.7(PTGES2):​c.893G>A​(p.Arg298His) variant causes a missense change. The variant allele was found at a frequency of 0.172 in 1,612,314 control chromosomes in the GnomAD database, including 27,448 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1673 hom., cov: 33)
  • Exomes 𝑓: 0.18 (25775 hom.)
• Consequence: PTGES2 NM_025072.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015058517).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGES2	NM_025072.7	c.893G>A	p.Arg298His	missense_variant	6/7	ENST00000338961.11	NP_079348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGES2	ENST00000338961.11	c.893G>A	p.Arg298His	missense_variant	6/7	1	NM_025072.7	ENSP00000345341.6

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19383 AN: 152186 Hom.: 1675 Cov.: 33

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0428

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.143

GnomAD3 exomes AF: 0.127 AC: 31881 AN: 250790 Hom.: 2678 AF XY: 0.128 AC XY: 17358 AN XY: 135584

Gnomad AFR exome AF: 0.0324

Gnomad AMR exome AF: 0.0928

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0421

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.177 AC: 257769 AN: 1460010 Hom.: 25775 Cov.: 32 AF XY: 0.173 AC XY: 125891 AN XY: 726452

Gnomad4 AFR exome AF: 0.0310

Gnomad4 AMR exome AF: 0.0972

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0436

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.127 AC: 19375 AN: 152304 Hom.: 1673 Cov.: 33 AF XY: 0.120 AC XY: 8947 AN XY: 74468

Gnomad4 AFR AF: 0.0360

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0429

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.141

Alfa AF: 0.181 Hom.: 5372

Bravo AF: 0.127

TwinsUK AF: 0.173 AC: 643

ALSPAC AF: 0.200 AC: 770

ESP6500AA AF: 0.0438 AC: 193

ESP6500EA AF: 0.197 AC: 1690

ExAC AF: 0.125 AC: 15212

Asia WGS AF: 0.0250 AC: 87 AN: 3478

EpiCase AF: 0.201

EpiControl AF: 0.207

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.77
DEOGEN2	Benign	0.066	T;.;.;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.83	T;.;T;T
MetaRNN	Benign	0.0015	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.92	N;.;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.69	N;.;N;N
REVEL	Benign	0.068
Sift	Benign	0.66	T;.;T;T
Sift4G	Benign	0.71	T;T;T;.
Polyphen		0.0010	B;.;.;.
Vest4		0.052
MPC		0.27
ClinPred		0.011	T
GERP RS		2.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.021
gMVP		0.22

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

Other links and lift over

dbSNP: rs13283456; hg19: chr9-130884753; COSMIC: COSV52968540; COSMIC: COSV52968540;