Genetic Variant PTGS2:n.2657T>C (chr1-186673926-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000963.4(PTGS2):c.*427T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,406 control chromosomes in the GnomAD database, including 13,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

Frequency

Genomes: 𝑓 0.40 ( 13771 hom., cov: 33)

Exomes 𝑓: 0.35 ( 18 hom. )

Consequence

PTGS2
NM_000963.4 3_prime_UTR

Scores

Clinical Significance

other no assertion criteria provided O:1

Conservation

PhyloP100: -1.15

Publications

331 publications found

Variant links:

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]

PTGS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS2	NM_000963.4 link	c.*427T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000367468.10	NP_000954.1	P35354

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGS2	ENST00000367468.10 link	c.*427T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_000963.4	ENSP00000356438.5		P35354

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61413

AN:

151922

Hom.:

13726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.607

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.365

GnomAD4 exome

AF:

0.347

AC:

127

AN:

366

Hom.:

Cov.:

AF XY:

0.357

AC XY:

AN XY:

224

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.341

AC:

105

AN:

308

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.405

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.405

AC:

61514

AN:

152040

Hom.:

13771

Cov.:

AF XY:

0.398

AC XY:

29605

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.608

AC:

25184

AN:

41452

American (AMR)

AF:

0.319

AC:

4878

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

1163

AN:

3464

East Asian (EAS)

AF:

0.192

AC:

993

AN:

5174

South Asian (SAS)

AF:

0.392

AC:

1893

AN:

4826

European-Finnish (FIN)

AF:

0.296

AC:

3125

AN:

10570

Middle Eastern (MID)

AF:

0.288

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.341

AC:

23202

AN:

67954

Other (OTH)

AF:

0.366

AC:

775

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1737

3474

5212

6949

8686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.366

Hom.:

26219

Bravo

AF:

0.412

Asia WGS

AF:

0.336

AC:

1165

AN:

3468

ClinVar

Significance: other

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Cholangiocarcinoma

Other:1

Dec 10, 2022

Department of Surgery, Campus Charité Mitte Campus Virchow-klinikum, Charite-Universitaetsmedizin Berlin

Significance:other

Review Status:no assertion criteria provided

Collection Method:research

No association with disease-free or overall survival after resection of intrahepatic Cholangiocarcinoma No association with disease-free or overall survival

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.96

(source)

DANN

Benign

0.38

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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1-186673926-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over