9-128122474-C-T

Variant names:

• chr9-128122474-C-T
• rs13283456
• NM_025072.7:c.893G>A

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 52 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025072.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES2	NM_025072.7	MANE Select	c.893G>A	p.Arg298His	missense	Exon 6 of 7	NP_079348.1	Q9H7Z7
	PTGES2	NM_001256335.2		c.320G>A	p.Arg107His	missense	Exon 7 of 8	NP_001243264.1	A6NHH0
	PTGES2	NM_198938.3		c.320G>A	p.Arg107His	missense	Exon 7 of 8	NP_945176.1	A6NHH0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES2	ENST00000338961.11	TSL:1 MANE Select	c.893G>A	p.Arg298His	missense	Exon 6 of 7	ENSP00000345341.6	Q9H7Z7
	PTGES2	ENST00000930205.1		c.1064G>A	p.Arg355His	missense	Exon 6 of 7	ENSP00000600264.1
	PTGES2	ENST00000930204.1		c.932G>A	p.Arg311His	missense	Exon 6 of 7	ENSP00000600263.1

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

GnomAD2 exomes AF: 0.127 AC: 31881 AN: 250790 AF XY: 0.128

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 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

African (AFR) AF: 0.0310 AC: 1038 AN: 33476

American (AMR) AF: 0.0972 AC: 4344 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 4480 AN: 26124

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39698

South Asian (SAS) AF: 0.0436 AC: 3759 AN: 86254

European-Finnish (FIN) AF: 0.106 AC: 5627 AN: 53212

Middle Eastern (MID) AF: 0.117 AC: 676 AN: 5766

European-Non Finnish (NFE) AF: 0.205 AC: 228134 AN: 1110448

Other (OTH) AF: 0.161 AC: 9702 AN: 60330

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

African (AFR) AF: 0.0360 AC: 1497 AN: 41568

American (AMR) AF: 0.127 AC: 1941 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0429 AC: 207 AN: 4830

European-Finnish (FIN) AF: 0.110 AC: 1165 AN: 10620

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13447 AN: 68008

Other (OTH) AF: 0.141 AC: 298 AN: 2110

Alfa AF: 0.170 Hom.: 7195

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 v4.9

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
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.92	N
PhyloP100		4.6
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.69	N
REVEL	Benign	0.068
Sift	Benign	0.66	T
Sift4G	Benign	0.71	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
Mutation Taster		=75/25	polymorphism (auto)

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

Other links and lift over

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