rs2745557

Variant names:

• chr1-186680089-A-G
• rs2745557
• NM_000963.4:c.52+150T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-186680089-A-G
• chr1-186680089-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000963.4(PTGS2):​c.52+150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 1,177,872 control chromosomes in the GnomAD database, including 403,665 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 0.83 (52975 hom., cov: 32)
  • Exomes 𝑓: 0.83 (350690 hom.)
• Consequence: PTGS2 NM_000963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433
• Publications: 76 publications found

Genes affected

PTGS2 (HGNC:9605): (prostaglandin-endoperoxide synthase 2) Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase, is the key enzyme in prostaglandin biosynthesis, and acts both as a dioxygenase and as a peroxidase. There are two isozymes of PTGS: a constitutive PTGS1 and an inducible PTGS2, which differ in their regulation of expression and tissue distribution. This gene encodes the inducible isozyme. It is regulated by specific stimulatory events, suggesting that it is responsible for the prostanoid biosynthesis involved in inflammation and mitogenesis. [provided by RefSeq, Feb 2009]

PACERR (HGNC:50552): (PTGS2 antisense NFKB1 complex-mediated expression regulator RNA) This gene represents transcription of a long non-coding RNA produced in antisense to the prostaglandin-endoperoxide synthase 2 (PTGS2) gene. This transcript interacts with NF-kB transcriptional regulators to promote expression of PTGS2. [provided by RefSeq, Feb 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000963.4. 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
	PTGS2	NM_000963.4	MANE Select	c.52+150T>C		intron	N/A	NP_000954.1	P35354

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	ENST00000367468.10	TSL:1 MANE Select	c.52+150T>C		intron	N/A	ENSP00000356438.5	P35354
	PTGS2	ENST00000490885.6	TSL:1	n.185+150T>C		intron	N/A
	PTGS2	ENST00000559627.1	TSL:1	n.52+150T>C		intron	N/A	ENSP00000454130.1	Q6ZYK7

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126784 AN: 152064 Hom.: 52923 Cov.: 32

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.800

GnomAD4 exome AF: 0.826 AC: 846768 AN: 1025690 Hom.: 350690 AF XY: 0.823 AC XY: 421916 AN XY: 512408

African (AFR) AF: 0.848 AC: 19416 AN: 22896

American (AMR) AF: 0.891 AC: 22379 AN: 25130

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 13835 AN: 18774

East Asian (EAS) AF: 0.961 AC: 31744 AN: 33024

South Asian (SAS) AF: 0.784 AC: 49120 AN: 62652

European-Finnish (FIN) AF: 0.826 AC: 36894 AN: 44676

Middle Eastern (MID) AF: 0.689 AC: 2899 AN: 4210

European-Non Finnish (NFE) AF: 0.824 AC: 633897 AN: 769414

Other (OTH) AF: 0.815 AC: 36584 AN: 44914

GnomAD4 genome AF: 0.834 AC: 126896 AN: 152182 Hom.: 52975 Cov.: 32 AF XY: 0.833 AC XY: 62000 AN XY: 74404

African (AFR) AF: 0.848 AC: 35224 AN: 41522

American (AMR) AF: 0.851 AC: 13023 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2614 AN: 3468

East Asian (EAS) AF: 0.964 AC: 4986 AN: 5170

South Asian (SAS) AF: 0.787 AC: 3797 AN: 4822

European-Finnish (FIN) AF: 0.826 AC: 8747 AN: 10588

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55886 AN: 67994

Other (OTH) AF: 0.802 AC: 1696 AN: 2116

Alfa AF: 0.825 Hom.: 39087

Bravo AF: 0.839

Asia WGS AF: 0.872 AC: 3033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.0
DANN	Benign	0.55
PhyloP100		-0.43
PromoterAI		-0.0033	Neutral
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: rs2745557; hg19: chr1-186649221;