11-73234469-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002564.4(P2RY2):​c.310G>T​(p.Val104Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V104M) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
• Consequence: P2RY2 NM_002564.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1025818).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002564.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RY2	NM_002564.4	MANE Select	c.310G>T	p.Val104Leu	missense	Exon 3 of 3	NP_002555.4
	P2RY2	NM_176071.3		c.310G>T	p.Val104Leu	missense	Exon 3 of 3	NP_788085.3	P41231
	P2RY2	NM_176072.3		c.310G>T	p.Val104Leu	missense	Exon 3 of 3	NP_788086.3	P41231

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RY2	ENST00000393597.7	TSL:1 MANE Select	c.310G>T	p.Val104Leu	missense	Exon 3 of 3	ENSP00000377222.2	P41231
	P2RY2	ENST00000311131.6	TSL:1	c.310G>T	p.Val104Leu	missense	Exon 3 of 3	ENSP00000310305.2	P41231
	P2RY2	ENST00000393596.2	TSL:1	c.310G>T	p.Val104Leu	missense	Exon 3 of 3	ENSP00000377221.2	P41231

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 56

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

African (AFR) AF: 0.0000241 AC: 1 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.78
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.32	N
PhyloP100		2.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.075
Sift	Benign	0.74	T
Sift4G	Benign	0.85	T
Polyphen		0.0030	B
Vest4		0.093
MutPred		0.52		Loss of ubiquitination at K107 (P = 0.1423)
MVP		0.78
MPC		0.34
ClinPred		0.13	T
GERP RS		3.4
Varity_R		0.068
gMVP		0.23
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs866940383; hg19: chr11-72945514;