14-52268109-G-T

Position:

• chr14-52268109-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000953.3(PTGDR):​c.295G>T​(p.Ala99Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTGDR NM_000953.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.161

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 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=0.049673617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGDR	NM_000953.3	c.295G>T	p.Ala99Ser	missense_variant	1/2	ENST00000306051.3	NP_000944.1
PTGDR	NM_001281469.2	c.295G>T	p.Ala99Ser	missense_variant	1/3		NP_001268398.1
PTGDR	XM_005267891.5	c.295G>T	p.Ala99Ser	missense_variant	1/3		XP_005267948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGDR	ENST00000306051.3	c.295G>T	p.Ala99Ser	missense_variant	1/2	1	NM_000953.3	ENSP00000303424.2
PTGDR	ENST00000553372.1	c.295G>T	p.Ala99Ser	missense_variant	1/3	3		ENSP00000452408.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Nov 14, 2024

The c.295G>T (p.A99S) alteration is located in exon 1 (coding exon 1) of the PTGDR gene. This alteration results from a G to T substitution at nucleotide position 295, causing the alanine (A) at amino acid position 99 to be replaced by a serine (S). 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	0.065
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.1
DANN	Benign	0.65
DEOGEN2	Benign	0.057	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.34	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.13	N;N
REVEL	Benign	0.016
Sift	Benign	0.46	T;T
Sift4G	Benign	0.82	T;T
Polyphen		0.036	B;.
Vest4		0.11
MutPred		0.43		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.14
MPC		0.47
ClinPred		0.075	T
GERP RS		-0.48
Varity_R		0.054
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-52734827;