NM_000956.4:c.179G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000956.4(PTGER2):​c.179G>A​(p.Arg60His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000883 in 1,584,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PTGER2
NM_000956.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

Publications

1 publications found
Variant links:
Genes affected
PTGER2 (HGNC:9594): (prostaglandin E receptor 2) This gene encodes a receptor for prostaglandin E2, a metabolite of arachidonic acid which has different biologic activities in a wide range of tissues. Mutations in this gene are associated with aspirin-induced susceptibility to asthma. [provided by RefSeq, Oct 2009]
PTGER2 Gene-Disease associations (from GenCC):
  • asthma, nasal polyps, and aspirin intolerance
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.048627466).
BS2
High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTGER2NM_000956.4 linkc.179G>A p.Arg60His missense_variant Exon 1 of 2 ENST00000245457.6 NP_000947.2 P43116

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTGER2ENST00000245457.6 linkc.179G>A p.Arg60His missense_variant Exon 1 of 2 1 NM_000956.4 ENSP00000245457.5 P43116
PTGER2ENST00000557436.2 linkc.-80+226G>A intron_variant Intron 1 of 2 3 ENSP00000450933.1 G3V2Y6
ENSG00000289424ENST00000726802.1 linkn.355+410C>T intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000257
AC:
6
AN:
233208
AF XY:
0.0000237
show subpopulations
Gnomad AFR exome
AF:
0.000392
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000209
AC:
3
AN:
1432632
Hom.:
0
Cov.:
33
AF XY:
0.00000141
AC XY:
1
AN XY:
708192
show subpopulations
African (AFR)
AF:
0.0000912
AC:
3
AN:
32908
American (AMR)
AF:
0.00
AC:
0
AN:
42946
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24596
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39146
South Asian (SAS)
AF:
0.00
AC:
0
AN:
83764
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51842
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5666
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1092812
Other (OTH)
AF:
0.00
AC:
0
AN:
58952
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.558
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74428
show subpopulations
African (AFR)
AF:
0.000265
AC:
11
AN:
41568
American (AMR)
AF:
0.00
AC:
0
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5148
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10608
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68000
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000540
Hom.:
0
Bravo
AF:
0.0000642
ESP6500AA
AF:
0.000228
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 20, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.179G>A (p.R60H) alteration is located in exon 1 (coding exon 1) of the PTGER2 gene. This alteration results from a G to A substitution at nucleotide position 179, causing the arginine (R) at amino acid position 60 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
17
DANN
Uncertain
0.97
DEOGEN2
Benign
0.25
T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.59
T
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.049
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N
PhyloP100
1.2
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.086
Sift
Benign
0.18
T
Sift4G
Benign
0.24
T
Polyphen
0.022
B
Vest4
0.097
MVP
0.40
MPC
0.89
ClinPred
0.059
T
GERP RS
4.9
PromoterAI
-0.030
Neutral
Varity_R
0.14
gMVP
0.49
Mutation Taster
=94/6
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

Other links and lift over

dbSNP: rs139726427; hg19: chr14-52781445; API