1-186679065-C-G

Variant names:

• chr1-186679065-C-G
• rs5277
• NM_000963.4:c.306G>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000963.4(PTGS2):​c.306G>C​(p.Val102Val) 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
• Publications: 110 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	NM_000963.4	MANE Select	c.306G>C	p.Val102Val	synonymous	Exon 3 of 10	NP_000954.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS2	ENST00000367468.10	TSL:1 MANE Select	c.306G>C	p.Val102Val	synonymous	Exon 3 of 10	ENSP00000356438.5
	PTGS2	ENST00000490885.6	TSL:1	n.439G>C		non_coding_transcript_exon	Exon 3 of 9
	PTGS2	ENST00000559627.1	TSL:1	n.306G>C		non_coding_transcript_exon	Exon 3 of 10	ENSP00000454130.1

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

GnomAD2 exomes AF: 0.120 AC: 29987 AN: 250388 AF XY: 0.124

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 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

African (AFR) AF: 0.0274 AC: 917 AN: 33430

American (AMR) AF: 0.0812 AC: 3619 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2782 AN: 26080

East Asian (EAS) AF: 0.0377 AC: 1496 AN: 39670

South Asian (SAS) AF: 0.0835 AC: 7189 AN: 86080

European-Finnish (FIN) AF: 0.169 AC: 9042 AN: 53406

Middle Eastern (MID) AF: 0.136 AC: 782 AN: 5756

European-Non Finnish (NFE) AF: 0.157 AC: 175032 AN: 1111332

Other (OTH) AF: 0.127 AC: 7694 AN: 60354

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

African (AFR) AF: 0.0318 AC: 1324 AN: 41570

American (AMR) AF: 0.123 AC: 1888 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3470

East Asian (EAS) AF: 0.0370 AC: 192 AN: 5188

South Asian (SAS) AF: 0.0779 AC: 375 AN: 4812

European-Finnish (FIN) AF: 0.181 AC: 1911 AN: 10582

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10968 AN: 68002

Other (OTH) AF: 0.114 AC: 241 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.5
DANN	Benign	0.74
PhyloP100		0.042
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: rs5277; hg19: chr1-186648197; COSMIC: COSV66568541; COSMIC: COSV66568541;