11-60852801-A-G

Position:

• chr11-60852801-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004778.3(PTGDR2):​c.922T>C​(p.Cys308Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000569 in 1,405,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: PTGDR2 NM_004778.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41438103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGDR2	NM_004778.3	c.922T>C	p.Cys308Arg	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.922T>C	p.Cys308Arg	missense_variant	2/2	1	NM_004778.3	ENSP00000332812.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000569 AC: 8 AN: 1405356 Hom.: 0 Cov.: 29 AF XY: 0.00000864 AC XY: 6 AN XY: 694486

Gnomad4 AFR exome AF: 0.0000320

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000399

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000184

Gnomad4 OTH exome AF: 0.0000344

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

Apr 25, 2023

The c.922T>C (p.C308R) alteration is located in exon 2 (coding exon 1) of the PTGDR2 gene. This alteration results from a T to C substitution at nucleotide position 922, causing the cysteine (C) at amino acid position 308 to be replaced by an arginine (R). 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	Pathogenic	0.83
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.18
Sift	Benign	0.15	T
Sift4G	Benign	0.10	T
Polyphen		0.77	P
Vest4		0.49
MutPred		0.65		Gain of MoRF binding (P = 0.0152);
MVP		0.51
MPC		2.6
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.82
gMVP		0.59

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: chr11-60620274;