14-52267833-C-T

Position:

• chr14-52267833-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000953.3(PTGDR):​c.19C>T​(p.Arg7Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,570,102 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.011 (29 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (34 hom.)
• Consequence: PTGDR NM_000953.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.103

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040405393).
• BP6: Variant 14-52267833-C-T is Benign according to our data. Variant chr14-52267833-C-T is described in ClinVar as [Benign]. Clinvar id is 790685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1669/152352) while in subpopulation AFR AF= 0.0342 (1424/41582). AF 95% confidence interval is 0.0328. There are 29 homozygotes in gnomad4. There are 807 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 29 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGDR	NM_000953.3	c.19C>T	p.Arg7Cys	missense_variant	1/2	ENST00000306051.3	NP_000944.1
PTGDR	NM_001281469.2	c.19C>T	p.Arg7Cys	missense_variant	1/3		NP_001268398.1
PTGDR	XM_005267891.5	c.19C>T	p.Arg7Cys	missense_variant	1/3		XP_005267948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGDR	ENST00000306051.3	c.19C>T	p.Arg7Cys	missense_variant	1/2	1	NM_000953.3	ENSP00000303424.2
PTGDR	ENST00000553372.1	c.19C>T	p.Arg7Cys	missense_variant	1/3	3		ENSP00000452408.1

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1663 AN: 152234 Hom.: 29 Cov.: 33

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00353 AC: 768 AN: 217588 Hom.: 15 AF XY: 0.00279 AC XY: 325 AN XY: 116696

Gnomad AFR exome AF: 0.0359

Gnomad AMR exome AF: 0.00419

Gnomad ASJ exome AF: 0.000148

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000130

Gnomad FIN exome AF: 0.0000540

Gnomad NFE exome AF: 0.000568

Gnomad OTH exome AF: 0.00385

GnomAD4 exome AF: 0.00151 AC: 2135 AN: 1417750 Hom.: 34 Cov.: 31 AF XY: 0.00134 AC XY: 939 AN XY: 699632

Gnomad4 AFR exome AF: 0.0381

Gnomad4 AMR exome AF: 0.00431

Gnomad4 ASJ exome AF: 0.0000434

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000190

Gnomad4 FIN exome AF: 0.000235

Gnomad4 NFE exome AF: 0.000390

Gnomad4 OTH exome AF: 0.00398

GnomAD4 genome AF: 0.0110 AC: 1669 AN: 152352 Hom.: 29 Cov.: 33 AF XY: 0.0108 AC XY: 807 AN XY: 74508

Gnomad4 AFR AF: 0.0342

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00279 Hom.: 52

Bravo AF: 0.0123

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0338 AC: 149

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00388 AC: 470

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 03, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.81	T;T
MetaRNN	Benign	0.0040	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.033	D;D
Polyphen		0.99	D;.
Vest4		0.51
MVP		0.33
MPC		1.1
ClinPred		0.028	T
GERP RS		2.5
Varity_R		0.078
gMVP		0.39

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: rs41311442; hg19: chr14-52734551;