1-186674636-A-T

Variant names:

• chr1-186674636-A-T
• rs5273
• NM_000963.4:c.1532T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000963.4(PTGS2):​c.1532T>A​(p.Val511Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTGS2 NM_000963.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.98
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1532T>A	p.Val511Asp	missense	Exon 10 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.1532T>A	p.Val511Asp	missense	Exon 10 of 10	ENSP00000356438.5
	PTGS2	ENST00000490885.6	TSL:1	n.1947T>A		non_coding_transcript_exon	Exon 9 of 9
	PTGS2	ENST00000559627.1	TSL:1	n.*930T>A		non_coding_transcript_exon	Exon 10 of 10	ENSP00000454130.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Uncertain	0.64	D
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.69	N
PhyloP100		6.0
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.083	B
Vest4		0.52
MutPred		0.46		Gain of disorder (P = 0.05)
MVP		0.89
MPC		1.6
ClinPred		0.98	D
GERP RS		3.3
Varity_R		0.91
gMVP		0.95
Mutation Taster		=62/38	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

Other links and lift over

dbSNP: rs5273; hg19: chr1-186643768;