14-52314630-A-G

Variant names:

• chr14-52314630-A-G
• NM_000956.4:c.82A>G

Variant summary

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

The NM_000956.4(PTGER2):​c.82A>G​(p.Ser28Gly) 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.41
• 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.82A>G	p.Ser28Gly	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.82A>G	p.Ser28Gly	missense_variant	Exon 1 of 2	1	NM_000956.4	ENSP00000245457.5
PTGER2	ENST00000557436.2	c.-80+129A>G		intron_variant	Intron 1 of 2	3		ENSP00000450933.1
ENSG00000289424	ENST00000726802.1	n.355+507T>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

Submissions by phenotype

not specified Uncertain:1

Dec 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.82A>G (p.S28G) 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 82, causing the serine (S) at amino acid position 28 to be replaced by a glycine (G). 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.4
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.19
Sift	Uncertain	0.012	D
Sift4G	Benign	0.24	T
Polyphen		1.0	D
Vest4		0.32
MutPred		0.43		Loss of sheet (P = 0.0315);
MVP		0.79
MPC		1.7
ClinPred		0.97	D
GERP RS		5.2
PromoterAI		0.047	Neutral
Varity_R		0.43
gMVP		0.60
Mutation Taster		=41/59	disease causing

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

hg19: chr14-52781348;