14-52268328-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000953.3(PTGDR):c.514G>A(p.Gly172Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000024 ( 0 hom. )
Consequence
PTGDR
NM_000953.3 missense
NM_000953.3 missense
Scores
8
6
5
Clinical Significance
Conservation
PhyloP100: 8.11
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.844
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTGDR | NM_000953.3 | c.514G>A | p.Gly172Arg | missense_variant | 1/2 | ENST00000306051.3 | |
PTGDR | NM_001281469.2 | c.514G>A | p.Gly172Arg | missense_variant | 1/3 | ||
PTGDR | XM_005267891.5 | c.514G>A | p.Gly172Arg | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTGDR | ENST00000306051.3 | c.514G>A | p.Gly172Arg | missense_variant | 1/2 | 1 | NM_000953.3 | P1 | |
PTGDR | ENST00000553372.1 | c.514G>A | p.Gly172Arg | missense_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152186Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000479 AC: 12AN: 250618Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135518
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GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461448Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727054
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152304Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74470
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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 | Jun 06, 2023 | The c.514G>A (p.G172R) alteration is located in exon 1 (coding exon 1) of the PTGDR gene. This alteration results from a G to A substitution at nucleotide position 514, causing the glycine (G) at amino acid position 172 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Benign
D;D
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MutPred
Gain of methylation at G172 (P = 0.0598);Gain of methylation at G172 (P = 0.0598);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at