Genetic Variant PTGER2:p.Met116Thr (chr14-52314895-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_000956.4(PTGER2):c.347T>C(p.Met116Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M116R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PTGER2
NM_000956.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.02

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

PTGER2 links:

ENSG00000289424 (HGNC:):

ENSG00000289424 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.827

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGER2	NM_000956.4 link	c.347T>C	p.Met116Thr	missense_variant	Exon 1 of 2	ENST00000245457.6	NP_000947.2	P43116

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTGER2	ENST00000245457.6 link	c.347T>C	p.Met116Thr	missense_variant	Exon 1 of 2	1	NM_000956.4	ENSP00000245457.5	P43116
PTGER2	ENST00000557436.2 link	c.-79-340T>C		intron_variant	Intron 1 of 2	3		ENSP00000450933.1	G3V2Y6
ENSG00000289424	ENST00000726802.1 link	n.355+242A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248244

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

6.85e-7

AC:

AN:

1460660

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726628

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.0000224

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52452

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111890

Other (OTH)

AF:

0.00

AC:

AN:

60380

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

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.59

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.093

MetaRNN

Pathogenic

0.83

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.4

PhyloP100

8.0

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-5.4

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.052

Polyphen

0.91

Vest4

0.89

MutPred

0.63

Loss of stability (P = 0.0606);

MVP

0.72

MPC

1.9

ClinPred

0.99

GERP RS

5.1

Varity_R

0.94

gMVP

0.84

Mutation Taster

=68/32

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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chr14-52314895-T-C

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