chr14-52314727-G-T

Variant names:

• chr14-52314727-G-T
• rs139726427
• NM_000956.4:c.179G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000956.4(PTGER2):​c.179G>T​(p.Arg60Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 1,584,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. R60H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PTGER2 NM_000956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18524787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGER2	NM_000956.4	c.179G>T	p.Arg60Leu	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.179G>T	p.Arg60Leu	missense_variant	Exon 1 of 2	1	NM_000956.4	ENSP00000245457.5
PTGER2	ENST00000557436.2	c.-80+226G>T		intron_variant	Intron 1 of 2	3		ENSP00000450933.1
ENSG00000289424	ENST00000726802.1	n.355+410C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152126 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: 0.00000209 AC: 3 AN: 1432634 Hom.: 0 Cov.: 33 AF XY: 0.00000141 AC XY: 1 AN XY: 708194

African (AFR) AF: 0.00 AC: 0 AN: 32908

American (AMR) AF: 0.00 AC: 0 AN: 42946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24596

East Asian (EAS) AF: 0.00 AC: 0 AN: 39146

South Asian (SAS) AF: 0.00 AC: 0 AN: 83764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51842

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5666

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1092814

Other (OTH) AF: 0.00 AC: 0 AN: 58952

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74300

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000540 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.072
Sift	Benign	0.12	T
Sift4G	Benign	0.067	T
Polyphen		0.22	B
Vest4		0.16
MutPred		0.57		Loss of methylation at R60 (P = 0.0137);
MVP		0.40
MPC		0.93
ClinPred		0.31	T
GERP RS		4.9
PromoterAI		0.0071	Neutral
Varity_R		0.31
gMVP		0.64
Mutation Taster		=88/12	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: rs139726427; hg19: chr14-52781445;