1-186679065-C-G

Position:

• chr1-186679065-C-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000963.4(PTGS2):​c.306G>C​(p.Val102=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,612,942 control chromosomes in the GnomAD database, including 17,422 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 0.11 (1296 hom., cov: 33)
  • Exomes 𝑓: 0.14 (16126 hom.)
• Consequence: PTGS2 NM_000963.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.042 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS2	NM_000963.4	c.306G>C	p.Val102=	synonymous_variant	3/10	ENST00000367468.10	NP_000954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000367468.10	c.306G>C	p.Val102=	synonymous_variant	3/10	1	NM_000963.4	ENSP00000356438	P1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17396 AN: 152120 Hom.: 1295 Cov.: 33

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0371

Gnomad SAS AF: 0.0785

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.120 AC: 29987 AN: 250388 Hom.: 2184 AF XY: 0.124 AC XY: 16736 AN XY: 135342

Gnomad AFR exome AF: 0.0302

Gnomad AMR exome AF: 0.0784

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.0392

Gnomad SAS exome AF: 0.0820

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.143 AC: 208553 AN: 1460704 Hom.: 16126 Cov.: 33 AF XY: 0.142 AC XY: 103113 AN XY: 726614

Gnomad4 AFR exome AF: 0.0274

Gnomad4 AMR exome AF: 0.0812

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.0377

Gnomad4 SAS exome AF: 0.0835

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.114 AC: 17389 AN: 152238 Hom.: 1296 Cov.: 33 AF XY: 0.114 AC XY: 8507 AN XY: 74422

Gnomad4 AFR AF: 0.0318

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0370

Gnomad4 SAS AF: 0.0779

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.114

Alfa AF: 0.117 Hom.: 447

Bravo AF: 0.105

Asia WGS AF: 0.0780 AC: 270 AN: 3478

EpiCase AF: 0.155

EpiControl AF: 0.161

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.5
DANN	Benign	0.74

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: rs5277; hg19: chr1-186648197; COSMIC: COSV66568541; COSMIC: COSV66568541;