Genetic Variant P2RY2:p.Arg318Pro (chr11-73235112-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_002564.4(P2RY2):c.953G>C(p.Arg318Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,470 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R318G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

P2RY2
NM_002564.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.70

Publications

0 publications found

Variant links:

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]

P2RY2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RY2	NM_002564.4 link	c.953G>C	p.Arg318Pro	missense_variant	Exon 3 of 3	ENST00000393597.7	NP_002555.4	P41231
P2RY2	NM_176071.3 link	c.953G>C	p.Arg318Pro	missense_variant	Exon 3 of 3		NP_788085.3	P41231
P2RY2	NM_176072.3 link	c.953G>C	p.Arg318Pro	missense_variant	Exon 3 of 3		NP_788086.3	P41231

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
P2RY2	ENST00000393597.7 link	c.953G>C	p.Arg318Pro	missense_variant	Exon 3 of 3	1	NM_002564.4	ENSP00000377222.2	P41231
P2RY2	ENST00000311131.6 link	c.953G>C	p.Arg318Pro	missense_variant	Exon 3 of 3	1		ENSP00000310305.2	P41231
P2RY2	ENST00000393596.2 link	c.953G>C	p.Arg318Pro	missense_variant	Exon 3 of 3	1		ENSP00000377221.2	P41231

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454470

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723598

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25942

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.00

AC:

AN:

86098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48216

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110518

Other (OTH)

AF:

0.00

AC:

AN:

60268

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;T;T

Eigen

Benign

-0.062

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.76

.;.;T

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.55

D;D;D

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.8

L;L;L

PhyloP100

2.7

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.24

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.016

D;D;D

Polyphen

0.83

P;P;P

Vest4

0.63

MutPred

0.53

Loss of MoRF binding (P = 0.0102);Loss of MoRF binding (P = 0.0102);Loss of MoRF binding (P = 0.0102);

MVP

0.69

MPC

0.86

ClinPred

0.83

GERP RS

3.3

Varity_R

0.44

gMVP

0.80

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over