14-52316377-G-T

Variant names:

• chr14-52316377-G-T
• rs45525634
• NM_000956.4:c.843+986G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000956.4(PTGER2):​c.843+986G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 152,272 control chromosomes in the GnomAD database, including 353 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.063 (353 hom., cov: 32)
• Consequence: PTGER2 NM_000956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGER2	NM_000956.4	c.843+986G>T		intron_variant	Intron 1 of 1	ENST00000245457.6	NP_000947.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGER2	ENST00000245457.6	c.843+986G>T		intron_variant	Intron 1 of 1	1	NM_000956.4	ENSP00000245457.5
PTGER2	ENST00000557436.2	c.78+986G>T		intron_variant	Intron 2 of 2	3		ENSP00000450933.1

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9531 AN: 152154 Hom.: 352 Cov.: 32

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0533

Gnomad ASJ AF: 0.0472

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00910

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0543

Gnomad OTH AF: 0.0621

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0626 AC: 9538 AN: 152272 Hom.: 353 Cov.: 32 AF XY: 0.0600 AC XY: 4464 AN XY: 74458

African (AFR) AF: 0.0974 AC: 4046 AN: 41530

American (AMR) AF: 0.0533 AC: 815 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0472 AC: 164 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00890 AC: 43 AN: 4830

European-Finnish (FIN) AF: 0.0584 AC: 620 AN: 10612

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0543 AC: 3697 AN: 68024

Other (OTH) AF: 0.0615 AC: 130 AN: 2114

Alfa AF: 0.0335 Hom.: 28

Bravo AF: 0.0642

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.51
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs45525634; hg19: chr14-52783095;