11-60852899-T-C

Position:

• chr11-60852899-T-C

Variant summary

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

The NM_004778.3(PTGDR2):​c.824A>G​(p.Asn275Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,375,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PTGDR2 NM_004778.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.266

Genes affected

PTGDR2 (HGNC:4502): (prostaglandin D2 receptor 2) This gene encodes a G-protein-coupled receptor that is preferentially expressed in CD4+ effector T helper 2 (Th2) cells. This protein is a prostaglandin D2 receptor that mediates the pro-inflammatory chemotaxis of eosinophils, basophils, and Th2 lymphocytes generated during allergic inflammation. Single nucleotide polymorphisms in the 3' UTR of this gene have been associated with asthma susceptibility.[provided by RefSeq, Mar 2011]

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=0.060653508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGDR2	NM_004778.3	c.824A>G	p.Asn275Ser	missense_variant	2/2	ENST00000332539.5	NP_004769.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGDR2	ENST00000332539.5	c.824A>G	p.Asn275Ser	missense_variant	2/2	1	NM_004778.3	ENSP00000332812.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1375330 Hom.: 0 Cov.: 29 AF XY: 0.00000295 AC XY: 2 AN XY: 677566

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000588

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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 23, 2023

The c.824A>G (p.N275S) alteration is located in exon 2 (coding exon 1) of the PTGDR2 gene. This alteration results from a A to G substitution at nucleotide position 824, causing the asparagine (N) at amino acid position 275 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	0.062
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.27
DANN	Benign	0.24
DEOGEN2	Benign	0.096	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.45	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.58	N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.095
Sift	Benign	1.0	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.023
MutPred		0.37		Gain of disorder (P = 0.059);
MVP		0.57
MPC		0.73
ClinPred		0.039	T
GERP RS		2.4
Varity_R		0.050
gMVP		0.12

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: rs763575164; hg19: chr11-60620372;