14-52268424-T-C

Position:

• chr14-52268424-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000953.3(PTGDR):​c.610T>C​(p.Ser204Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTGDR NM_000953.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.01

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGDR	NM_000953.3	c.610T>C	p.Ser204Pro	missense_variant	1/2	ENST00000306051.3	NP_000944.1
PTGDR	NM_001281469.2	c.610T>C	p.Ser204Pro	missense_variant	1/3		NP_001268398.1
PTGDR	XM_005267891.5	c.610T>C	p.Ser204Pro	missense_variant	1/3		XP_005267948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGDR	ENST00000306051.3	c.610T>C	p.Ser204Pro	missense_variant	1/2	1	NM_000953.3	ENSP00000303424.2
PTGDR	ENST00000553372.1	c.610T>C	p.Ser204Pro	missense_variant	1/3	3		ENSP00000452408.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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 28, 2024

The c.610T>C (p.S204P) alteration is located in exon 1 (coding exon 1) of the PTGDR gene. This alteration results from a T to C substitution at nucleotide position 610, causing the serine (S) at amino acid position 204 to be replaced by a proline (P). 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	0.54
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.
Eigen	Benign	0.021
Eigen_PC	Benign	0.028
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.29
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.86	P;.
Vest4		0.60
MutPred		0.74		Loss of catalytic residue at S204 (P = 0.014);Loss of catalytic residue at S204 (P = 0.014);
MVP		0.62
MPC		0.94
ClinPred		0.97	D
GERP RS		2.5
Varity_R		0.86
gMVP		0.78

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: rs1594617286; hg19: chr14-52735142;