9-128125577-C-T

Variant names:

• chr9-128125577-C-T
• rs884115
• NM_025072.7:c.280-136G>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.280-136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 805,602 control chromosomes in the GnomAD database, including 17,448 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (7539 hom., cov: 32)
  • Exomes 𝑓: 0.15 (9909 hom.)
• Consequence: PTGES2 NM_025072.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.82
• Publications: 17 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 (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES2	NM_025072.7	MANE Select	c.280-136G>A		intron	N/A	NP_079348.1
	PTGES2	NM_001256335.2		c.-198-136G>A		intron	N/A	NP_001243264.1
	PTGES2	NM_198938.3		c.-387-136G>A		intron	N/A	NP_945176.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES2	ENST00000338961.11	TSL:1 MANE Select	c.280-136G>A		intron	N/A	ENSP00000345341.6
	PTGES2	ENST00000930205.1		c.280-136G>A		intron	N/A	ENSP00000600264.1
	PTGES2	ENST00000930204.1		c.280-136G>A		intron	N/A	ENSP00000600263.1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38684 AN: 151826 Hom.: 7499 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.0929

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.149 AC: 97603 AN: 653658 Hom.: 9909 AF XY: 0.151 AC XY: 51050 AN XY: 338402

African (AFR) AF: 0.555 AC: 9295 AN: 16740

American (AMR) AF: 0.230 AC: 5994 AN: 26030

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 3075 AN: 16180

East Asian (EAS) AF: 0.235 AC: 7594 AN: 32304

South Asian (SAS) AF: 0.227 AC: 12192 AN: 53610

European-Finnish (FIN) AF: 0.0939 AC: 3039 AN: 32356

Middle Eastern (MID) AF: 0.232 AC: 555 AN: 2394

European-Non Finnish (NFE) AF: 0.114 AC: 50312 AN: 441036

Other (OTH) AF: 0.168 AC: 5547 AN: 33008

GnomAD4 genome AF: 0.255 AC: 38779 AN: 151944 Hom.: 7539 Cov.: 32 AF XY: 0.254 AC XY: 18872 AN XY: 74266

African (AFR) AF: 0.550 AC: 22755 AN: 41368

American (AMR) AF: 0.221 AC: 3384 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3470

East Asian (EAS) AF: 0.179 AC: 924 AN: 5156

South Asian (SAS) AF: 0.231 AC: 1112 AN: 4818

European-Finnish (FIN) AF: 0.0929 AC: 985 AN: 10600

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8200 AN: 67936

Other (OTH) AF: 0.249 AC: 525 AN: 2112

Alfa AF: 0.156 Hom.: 1597

Bravo AF: 0.276

Asia WGS AF: 0.255 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.29
DANN	Benign	0.28
PhyloP100		-3.8
Mutation Taster		=100/0	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: rs884115; hg19: chr9-130887856;