rs3218625

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000367468.10(PTGS2):​c.1759G>A​(p.Gly587Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000491 in 1,613,804 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00064 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00048 ( 4 hom. )

Consequence

PTGS2
ENST00000367468.10 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.327
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0026129186).
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000644 (98/152126) while in subpopulation EAS AF= 0.018 (93/5180). AF 95% confidence interval is 0.015. There are 1 homozygotes in gnomad4. There are 54 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 98 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTGS2NM_000963.4 linkuse as main transcriptc.1759G>A p.Gly587Arg missense_variant 10/10 ENST00000367468.10 NP_000954.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTGS2ENST00000367468.10 linkuse as main transcriptc.1759G>A p.Gly587Arg missense_variant 10/101 NM_000963.4 ENSP00000356438 P1

Frequencies

GnomAD3 genomes
AF:
0.000645
AC:
98
AN:
152008
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0179
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00163
AC:
409
AN:
251448
Hom.:
3
AF XY:
0.00146
AC XY:
199
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0219
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000475
AC:
695
AN:
1461678
Hom.:
4
Cov.:
30
AF XY:
0.000441
AC XY:
321
AN XY:
727150
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0163
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.000431
GnomAD4 genome
AF:
0.000644
AC:
98
AN:
152126
Hom.:
1
Cov.:
33
AF XY:
0.000726
AC XY:
54
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0180
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000618
Hom.:
0
Bravo
AF:
0.000884
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.00168
AC:
204
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.60
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
6.4
DANN
Benign
0.60
DEOGEN2
Benign
0.15
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.074
N
LIST_S2
Benign
0.62
T
MetaRNN
Benign
0.0026
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.20
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.12
N
REVEL
Benign
0.036
Sift
Benign
0.51
T
Sift4G
Benign
0.60
T
Polyphen
0.012
B
Vest4
0.079
MutPred
0.10
Gain of catalytic residue at G587 (P = 0.0059);
MVP
0.18
MPC
0.78
ClinPred
0.0032
T
GERP RS
-3.3
Varity_R
0.066
gMVP
0.74

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3218625; hg19: chr1-186643541; COSMIC: COSV66572041; COSMIC: COSV66572041; API