rs5277

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-186679065-C-A
• chr1-186679065-C-G
• chr1-186679065-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_000963.4(PTGS2):​c.306G>T​(p.Val102Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,066 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=0.042 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS2	NM_000963.4	c.306G>T	p.Val102Val	synonymous_variant	Exon 3 of 10	ENST00000367468.10	NP_000954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000367468.10	c.306G>T	p.Val102Val	synonymous_variant	Exon 3 of 10	1	NM_000963.4	ENSP00000356438.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461066 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726796

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33434

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44604

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26084

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39670

Gnomad4 SAS exome AF: 0.0000116 AC: 1 AN: 86084

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53406

Gnomad4 NFE exome AF: 0.00 AC: 0 AN: 1111658

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	7.7
DANN	Benign	0.81
Mutation Taster		=100/0	polymorphism

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;