chr11-60852983-A-G

Position:

• chr11-60852983-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004778.3(PTGDR2):​c.740T>C​(p.Leu247Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000799 in 1,252,278 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: not found (cov: 33)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: PTGDR2 NM_004778.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.56

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.937

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGDR2	NM_004778.3	c.740T>C	p.Leu247Pro	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.740T>C	p.Leu247Pro	missense_variant	2/2	1	NM_004778.3	ENSP00000332812.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.99e-7 AC: 1 AN: 1252278 Hom.: 0 Cov.: 29 AF XY: 0.00000164 AC XY: 1 AN XY: 610174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.87e-7

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

Jul 12, 2023

The c.740T>C (p.L247P) 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 740, causing the leucine (L) at amino acid position 247 to be replaced by a proline (P). 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	0.68
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	D
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.83	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.24	B
Vest4		0.55
MutPred		0.80		Loss of helix (P = 0.0167);
MVP		0.63
MPC		2.5
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.95
gMVP		0.89

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: chr11-60620456;