chr14-52314553-G-A

Variant names:

• chr14-52314553-G-A
• rs1200881425
• NM_000956.4:c.5G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_000956.4(PTGER2):​c.5G>A​(p.Gly2Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000939 in 1,491,298 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: PTGER2 NM_000956.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.515
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17027506).
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGER2	NM_000956.4	c.5G>A	p.Gly2Asp	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.5G>A	p.Gly2Asp	missense_variant	Exon 1 of 2	1	NM_000956.4	ENSP00000245457.5
PTGER2	ENST00000557436.2	c.-80+52G>A		intron_variant	Intron 1 of 2	3		ENSP00000450933.1
ENSG00000289424	ENST00000726802.1	n.355+584C>T		intron_variant	Intron 1 of 1
ENSG00000289424	ENST00000726803.1	n.-179C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000971 AC: 13 AN: 1339122 Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 9 AN XY: 653068

African (AFR) AF: 0.00 AC: 0 AN: 29608

American (AMR) AF: 0.00 AC: 0 AN: 25468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19422

East Asian (EAS) AF: 0.00 AC: 0 AN: 36974

South Asian (SAS) AF: 0.0000919 AC: 6 AN: 65316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5210

European-Non Finnish (NFE) AF: 0.00000570 AC: 6 AN: 1053404

Other (OTH) AF: 0.0000182 AC: 1 AN: 54852

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5G>A (p.G2D) 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 5, causing the glycine (G) at amino acid position 2 to be replaced by an aspartic acid (D). 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	0.074
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.098	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.92	L
PhyloP100		0.52
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.24
Sift	Benign	0.37	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.058		Gain of phosphorylation at S5 (P = 0.1655);
MVP		0.79
MPC		0.92
ClinPred		0.23	T
GERP RS		3.5
PromoterAI		0.057	Neutral
Varity_R		0.056
gMVP		0.39
Mutation Taster		=92/8	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: rs1200881425; hg19: chr14-52781271;