11-73234469-G-A

Variant names:

• chr11-73234469-G-A
• rs866940383
• NM_002564.4:c.310G>A

Variant summary

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

The NM_002564.4(P2RY2):​c.310G>A​(p.Val104Met) 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 benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: P2RY2 NM_002564.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98

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=0.33436164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RY2	NM_002564.4	c.310G>A	p.Val104Met	missense_variant	Exon 3 of 3	ENST00000393597.7	NP_002555.4
P2RY2	NM_176071.3	c.310G>A	p.Val104Met	missense_variant	Exon 3 of 3		NP_788085.3
P2RY2	NM_176072.3	c.310G>A	p.Val104Met	missense_variant	Exon 3 of 3		NP_788086.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RY2	ENST00000393597.7	c.310G>A	p.Val104Met	missense_variant	Exon 3 of 3	1	NM_002564.4	ENSP00000377222.2
P2RY2	ENST00000311131.6	c.310G>A	p.Val104Met	missense_variant	Exon 3 of 3	1		ENSP00000310305.2
P2RY2	ENST00000393596.2	c.310G>A	p.Val104Met	missense_variant	Exon 3 of 3	1		ENSP00000377221.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.310G>A (p.V104M) alteration is located in exon 3 (coding exon 1) of the P2RY2 gene. This alteration results from a G to A substitution at nucleotide position 310, causing the valine (V) at amino acid position 104 to be replaced by a methionine (M). 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	0.13
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T;T;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.056
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.95	.;.;D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.3	L;L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.48	N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.77	P;P;P
Vest4		0.31
MutPred		0.57		Gain of catalytic residue at V104 (P = 0.01);Gain of catalytic residue at V104 (P = 0.01);Gain of catalytic residue at V104 (P = 0.01);
MVP		0.86
MPC		0.59
ClinPred		0.59	D
GERP RS		3.4
Varity_R		0.058
gMVP		0.21

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: rs866940383; hg19: chr11-72945514; COSMIC: COSV105137145; COSMIC: COSV105137145;