NM_000956.4:c.370A>G

Variant summary

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

The NM_000956.4(PTGER2):​c.370A>G​(p.Met124Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PTGER2
NM_000956.4 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

Publications

0 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

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTGER2NM_000956.4 linkc.370A>G p.Met124Val 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.370A>G p.Met124Val missense_variant Exon 1 of 2 1 NM_000956.4 ENSP00000245457.5 P43116
PTGER2ENST00000557436.2 linkc.-79-317A>G intron_variant Intron 1 of 2 3 ENSP00000450933.1 G3V2Y6
ENSG00000289424ENST00000726802.1 linkn.355+219T>C intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 05, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.370A>G (p.M124V) alteration is located in exon 1 (coding exon 1) of the PTGER2 gene. This alteration results from a A to G substitution at nucleotide position 370, causing the methionine (M) at amino acid position 124 to be replaced by a valine (V). 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
0.30
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.10
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.23
T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.82
T
M_CAP
Uncertain
0.087
D
MetaRNN
Uncertain
0.73
D
MetaSVM
Benign
-0.32
T
MutationAssessor
Uncertain
2.8
M
PhyloP100
2.2
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.7
N
REVEL
Uncertain
0.40
Sift
Uncertain
0.028
D
Sift4G
Benign
0.10
T
Polyphen
0.86
P
Vest4
0.67
MutPred
0.42
Gain of catalytic residue at M124 (P = 0.0554);
MVP
0.84
MPC
1.6
ClinPred
0.95
D
GERP RS
5.1
Varity_R
0.59
gMVP
0.76
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

Publications

Other links and lift over

hg19: chr14-52781636; API