NM_000956.4:c.98C>G

Variant names:

• chr14-52314646-C-G
• rs753095269
• NM_000956.4:c.98C>G

Variant summary

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

The NM_000956.4(PTGER2):​c.98C>G​(p.Ser33Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000733 in 1,364,468 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S33L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PTGER2 NM_000956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 0 publications found

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

ENSG00000289424 (HGNC:):

ACMG classification

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
PTGER2	NM_000956.4	c.98C>G	p.Ser33Trp	missense_variant	Exon 1 of 2	ENST00000245457.6	NP_000947.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGER2	ENST00000245457.6	c.98C>G	p.Ser33Trp	missense_variant	Exon 1 of 2	1	NM_000956.4	ENSP00000245457.5
PTGER2	ENST00000557436.2	c.-80+145C>G		intron_variant	Intron 1 of 2	3		ENSP00000450933.1
ENSG00000289424	ENST00000726802.1	n.355+491G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.33e-7 AC: 1 AN: 1364468 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 667582

African (AFR) AF: 0.00 AC: 0 AN: 30328

American (AMR) AF: 0.00 AC: 0 AN: 29686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19948

East Asian (EAS) AF: 0.00 AC: 0 AN: 38696

South Asian (SAS) AF: 0.00 AC: 0 AN: 70754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5296

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1064098

Other (OTH) AF: 0.0000178 AC: 1 AN: 56098

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D
Eigen	Benign	0.15
Eigen_PC	Benign	0.073
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.077
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.12
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.040	D
Polyphen		0.99	D
Vest4		0.59
MutPred		0.58		Loss of sheet (P = 0.003);
MVP		0.64
MPC		1.9
ClinPred		0.98	D
GERP RS		3.2
PromoterAI		-0.041	Neutral
Varity_R		0.17
gMVP		0.67
Mutation Taster		=80/20	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

Other links and lift over

dbSNP: rs753095269; hg19: chr14-52781364;