Genetic Variant PTGS2:c.*2288G>A (chr1-186672065-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000963.4(PTGS2):c.*2288G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 151,718 control chromosomes in the GnomAD database, including 40 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 0.016 ( 40 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

PTGS2
NM_000963.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.478

Publications

10 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=-0.83).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0165 (2500/151718) while in subpopulation SAS AF = 0.0249 (120/4816). AF 95% confidence interval is 0.0217. There are 40 homozygotes in GnomAd4. There are 1237 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2500 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGS2	NM_000963.4 link	c.*2288G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000367468.10	NP_000954.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
PTGS2	ENST00000367468.10 link	c.*2288G>A	3_prime_UTR_variant	Exon 10 of 10	1	NM_000963.4	ENSP00000356438.5
PTGS2	ENST00000681605.1 link	n.*3775G>A	non_coding_transcript_exon_variant	Exon 10 of 10			ENSP00000504900.1
PTGS2	ENST00000680451.1 link	c.*2288G>A	3_prime_UTR_variant	Exon 11 of 11			ENSP00000506242.1
PTGS2	ENST00000681605.1 link	n.*3775G>A	3_prime_UTR_variant	Exon 10 of 10			ENSP00000504900.1

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2498

AN:

151602

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00588

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.0243

Gnomad EAS

AF:

0.00232

Gnomad SAS

AF:

0.0249

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0227

Gnomad OTH

AF:

0.0250

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0165

AC:

2500

AN:

151718

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1237

AN XY:

74112

show subpopulations

African (AFR)

AF:

0.00596

AC:

247

AN:

41438

American (AMR)

AF:

0.0156

AC:

238

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.0243

AC:

AN:

3462

East Asian (EAS)

AF:

0.00232

AC:

AN:

5170

South Asian (SAS)

AF:

0.0249

AC:

120

AN:

4816

European-Finnish (FIN)

AF:

0.0153

AC:

160

AN:

10450

Middle Eastern (MID)

AF:

0.0240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0226

AC:

1536

AN:

67858

Other (OTH)

AF:

0.0247

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

115

231

346

462

577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00944

Hom.:

Bravo

AF:

0.0155

Asia WGS

AF:

0.0130

AC:

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.79

(source)

DANN

Benign

0.57

PhyloP100

-0.48

Mutation Taster

=100/0

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over