14-52268104-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000953.3(PTGDR):c.290C>T(p.Ala97Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000366 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: PTGDR NM_000953.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.78

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0075412095).
• BP6: Variant 14-52268104-C-T is Benign according to our data. Variant chr14-52268104-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2226420.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGDR	NM_000953.3	c.290C>T	p.Ala97Val	missense_variant	1/2	ENST00000306051.3
PTGDR	NM_001281469.2	c.290C>T	p.Ala97Val	missense_variant	1/3
PTGDR	XM_005267891.5	c.290C>T	p.Ala97Val	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGDR	ENST00000306051.3	c.290C>T	p.Ala97Val	missense_variant	1/2	1	NM_000953.3	P1
PTGDR	ENST00000553372.1	c.290C>T	p.Ala97Val	missense_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152252 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000964

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000426 AC: 107 AN: 251278 Hom.: 0 AF XY: 0.000434 AC XY: 59 AN XY: 135846

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00575

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000369

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000376 AC: 549 AN: 1461624 Hom.: 0 Cov.: 31 AF XY: 0.000360 AC XY: 262 AN XY: 727142

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00570

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000316

Gnomad4 OTH exome AF: 0.000646

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152252 Hom.: 0 Cov.: 33 AF XY: 0.000269 AC XY: 20 AN XY: 74384

Gnomad4 AFR AF: 0.0000964

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000512 Hom.: 0

Bravo AF: 0.000325

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000371 AC: 45

EpiCase AF: 0.000382

EpiControl AF: 0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 05, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	0.034
Dann	Benign	0.86
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.0075	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.055	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.047
Sift	Benign	0.10	T;T
Sift4G	Benign	0.37	T;T
Polyphen		0.0060	B;.
Vest4		0.088
MVP		0.20
MPC		0.32
ClinPred		0.012	T
GERP RS		-7.3
Varity_R		0.034
gMVP		0.20

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: rs141737848; hg19: chr14-52734822;