chr11-60853095-T-C

Position:

• chr11-60853095-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004778.3(PTGDR2):​c.628A>G​(p.Lys210Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: PTGDR2 NM_004778.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.748

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGDR2	NM_004778.3	c.628A>G	p.Lys210Glu	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.628A>G	p.Lys210Glu	missense_variant	2/2	1	NM_004778.3	ENSP00000332812.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Jan 17, 2024

The c.628A>G (p.K210E) 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 628, causing the lysine (K) at amino acid position 210 to be replaced by a glutamic acid (E). 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	0.95
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.61	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.57
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.016	D
Polyphen		0.99	D
Vest4		0.40
MutPred		0.63		Loss of ubiquitination at K210 (P = 0.027);
MVP		0.83
MPC		2.4
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.75
gMVP		0.77

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: chr11-60620568;