14-52267968-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000953.3(PTGDR):c.154C>T(p.Arg52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,046 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PTGDR NM_000953.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.07

Genes affected

PTGDR (HGNC:9591): (prostaglandin D2 receptor) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) superfamily. The receptors are seven-pass transmembrane proteins that respond to extracellular cues and activate intracellular signal transduction pathways. This protein is reported to be a receptor for prostaglandin D2, which is a mediator of allergic inflammation and allergic airway inflammation in asthma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGDR	NM_000953.3	c.154C>T	p.Arg52Cys	missense_variant	1/2	ENST00000306051.3
PTGDR	NM_001281469.2	c.154C>T	p.Arg52Cys	missense_variant	1/3
PTGDR	XM_005267891.5	c.154C>T	p.Arg52Cys	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGDR	ENST00000306051.3	c.154C>T	p.Arg52Cys	missense_variant	1/2	1	NM_000953.3	P1
PTGDR	ENST00000553372.1	c.154C>T	p.Arg52Cys	missense_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457046 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725096

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2023

The c.154C>T (p.R52C) alteration is located in exon 1 (coding exon 1) of the PTGDR gene. This alteration results from a C to T substitution at nucleotide position 154, causing the arginine (R) at amino acid position 52 to be replaced by a cysteine (C). 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	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	19
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.0067	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	0.54	N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.027	D;D
Polyphen		1.0	D;.
Vest4		0.096
MutPred		0.74		Loss of MoRF binding (P = 0.0547);Loss of MoRF binding (P = 0.0547);
MVP		0.44
MPC		1.1
ClinPred		0.78	D
GERP RS		3.0
Varity_R		0.20
gMVP		0.40

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

Other links and lift over

dbSNP: rs1005575850; hg19: chr14-52734686;