Variant 11-60852911-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004778.3(PTGDR2):c.812G>A(p.Arg271Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000977 in 1,514,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

PTGDR2
NM_004778.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.02

Variant links:

Genes affected

PTGDR2 (HGNC:4502): (prostaglandin D2 receptor 2) This gene encodes a G-protein-coupled receptor that is preferentially expressed in CD4+ effector T helper 2 (Th2) cells. This protein is a prostaglandin D2 receptor that mediates the pro-inflammatory chemotaxis of eosinophils, basophils, and Th2 lymphocytes generated during allergic inflammation. Single nucleotide polymorphisms in the 3' UTR of this gene have been associated with asthma susceptibility.[provided by RefSeq, Mar 2011]

PTGDR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014074951).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGDR2	NM_004778.3 linkuse as main transcript	c.812G>A	p.Arg271Gln	missense_variant	2/2	ENST00000332539.5	NP_004769.2	Q9Y5Y4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGDR2	ENST00000332539.5 linkuse as main transcript	c.812G>A	p.Arg271Gln	missense_variant	2/2	1	NM_004778.3	ENSP00000332812.4		Q9Y5Y4

Frequencies

GnomAD3 genomes

AF:

0.000448

AC:

AN:

151766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000128

AC:

AN:

117626

Hom.:

AF XY:

0.0000933

AC XY:

AN XY:

64304

show subpopulations

Gnomad AFR exome

AF:

0.00229

Gnomad AMR exome

AF:

0.0000949

Gnomad ASJ exome

AF:

0.000822

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000244

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000587

AC:

AN:

1362456

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

670542

show subpopulations

Gnomad4 AFR exome

AF:

0.00156

Gnomad4 AMR exome

AF:

0.0000609

Gnomad4 ASJ exome

AF:

0.000710

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000566

Gnomad4 OTH exome

AF:

0.000178

GnomAD4 genome

AF:

0.000448

AC:

AN:

151874

Hom.:

Cov.:

AF XY:

0.000431

AC XY:

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000684

Hom.:

Bravo

AF:

0.000555

ExAC

AF:

0.0000551

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2024

The c.812G>A (p.R271Q) alteration is located in exon 2 (coding exon 1) of the PTGDR2 gene. This alteration results from a G to A substitution at nucleotide position 812, causing the arginine (R) at amino acid position 271 to be replaced by a glutamine (Q). 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

0.075

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.090

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.59

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.20

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.18

REVEL

Benign

0.074

Sift

Benign

0.62

Sift4G

Benign

0.58

Polyphen

0.11

Vest4

0.030

MutPred

0.67

Loss of methylation at R271 (P = 0.0099);

MVP

0.37

MPC

1.1

ClinPred

0.023

GERP RS

3.5

Varity_R

0.12

gMVP

0.19

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over