rs13283456

Positions:

• chr9-128122474-C-A
• chr9-128122474-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025072.7(PTGES2):​c.893G>T​(p.Arg298Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R298H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19953391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGES2	NM_025072.7	c.893G>T	p.Arg298Leu	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>T	p.Arg298Leu	missense_variant	6/7	1	NM_025072.7	ENSP00000345341	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250790 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135584

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461320 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727010

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;.;.;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.94	D;.;D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N;.;.;.
MutationTaster	Benign	0.72	D;D
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.5	D;.;D;D
REVEL	Benign	0.069
Sift	Benign	0.081	T;.;T;T
Sift4G	Benign	0.088	T;T;T;.
Polyphen		0.22	B;.;.;.
Vest4		0.29
MutPred		0.37		Loss of MoRF binding (P = 0.0205);.;.;.;
MVP		0.40
MPC		0.31
ClinPred		0.35	T
GERP RS		2.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.15
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;