11-73235019-C-T

Position:

• chr11-73235019-C-T

Variant summary

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

The NM_002564.4(P2RY2):​c.860C>T​(p.Ala287Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: P2RY2 NM_002564.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13

Genes affected

P2RY2 (HGNC:8541): (purinergic receptor P2Y2) The product of this gene belongs to the family of P2 receptors, which is activated by extracellular nucleotides and subdivided into P2X ligand-gated ion channels and P2Y G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor, found on many cell types, is activated by ATP and UTP and is reported to be overexpressed on some cancer cell types. It is involved in many cellular functions, such as proliferation, apoptosis and inflammation. Three transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Mar 2013]

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=0.31231344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RY2	NM_002564.4	c.860C>T	p.Ala287Val	missense_variant	3/3	ENST00000393597.7	NP_002555.4
P2RY2	NM_176071.3	c.860C>T	p.Ala287Val	missense_variant	3/3		NP_788085.3
P2RY2	NM_176072.3	c.860C>T	p.Ala287Val	missense_variant	3/3		NP_788086.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RY2	ENST00000393597.7	c.860C>T	p.Ala287Val	missense_variant	3/3	1	NM_002564.4	ENSP00000377222.2
P2RY2	ENST00000311131.6	c.860C>T	p.Ala287Val	missense_variant	3/3	1		ENSP00000310305.2
P2RY2	ENST00000393596.2	c.860C>T	p.Ala287Val	missense_variant	3/3	1		ENSP00000377221.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

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

Nov 11, 2024

The c.860C>T (p.A287V) alteration is located in exon 3 (coding exon 1) of the P2RY2 gene. This alteration results from a C to T substitution at nucleotide position 860, causing the alanine (A) at amino acid position 287 to be replaced by a valine (V). 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	0.24
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	T;T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	.;.;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;M;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.44	B;B;B
Vest4		0.27
MutPred		0.66		Gain of methylation at K289 (P = 0.0642);Gain of methylation at K289 (P = 0.0642);Gain of methylation at K289 (P = 0.0642);
MVP		0.90
MPC		0.44
ClinPred		0.93	D
GERP RS		3.3
Varity_R		0.29
gMVP		0.67

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: rs1651772951; hg19: chr11-72946064;