rs2745557

Positions:

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

Variant summary

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

The ENST00000367468.10(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 ENST00000367468.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS2	NM_000963.4	c.52+150T>C		intron_variant		ENST00000367468.10	NP_000954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000367468.10	c.52+150T>C		intron_variant		1	NM_000963.4	ENSP00000356438	P1

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

Gnomad4 AFR exome AF: 0.848

Gnomad4 AMR exome AF: 0.891

Gnomad4 ASJ exome AF: 0.737

Gnomad4 EAS exome AF: 0.961

Gnomad4 SAS exome AF: 0.784

Gnomad4 FIN exome AF: 0.826

Gnomad4 NFE exome AF: 0.824

Gnomad4 OTH exome AF: 0.815

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

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.964

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.822

Gnomad4 OTH AF: 0.802

Alfa AF: 0.825 Hom.: 24980

Bravo AF: 0.839

Asia WGS AF: 0.872 AC: 3033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.0
DANN	Benign	0.55

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: rs2745557; hg19: chr1-186649221;