Genetic Variant P2RY2:p.Arg312Ser (chr11-73235095-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002564.4(P2RY2):c.936G>T(p.Arg312Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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: 2.02

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:

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ACMG classification

Classification was made for transcript

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=0.13093096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RY2	NM_002564.4 link	c.936G>T	p.Arg312Ser	missense_variant	Exon 3 of 3	ENST00000393597.7	NP_002555.4	P41231
P2RY2	NM_176071.3 link	c.936G>T	p.Arg312Ser	missense_variant	Exon 3 of 3		NP_788085.3	P41231
P2RY2	NM_176072.3 link	c.936G>T	p.Arg312Ser	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.936G>T	p.Arg312Ser	missense_variant	Exon 3 of 3	1	NM_002564.4	ENSP00000377222.2	P41231
P2RY2	ENST00000311131.6 link	c.936G>T	p.Arg312Ser	missense_variant	Exon 3 of 3	1		ENSP00000310305.2	P41231
P2RY2	ENST00000393596.2 link	c.936G>T	p.Arg312Ser	missense_variant	Exon 3 of 3	1		ENSP00000377221.2	P41231

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454612

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723772

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:

33460

American (AMR)

AF:

0.00

AC:

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26026

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86166

European-Finnish (FIN)

AF:

0.0000209

AC:

AN:

47872

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110798

Other (OTH)

AF:

0.00

AC:

AN:

60260

⚠️ 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: 0.275

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

Uncertain

0.51

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.049

T;T;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.69

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.75

.;.;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;L

PhyloP100

2.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.52

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.095

T;T;T

Sift4G

Benign

0.15

T;T;T

Polyphen

0.015

B;B;B

Vest4

0.23

MutPred

0.45

Loss of MoRF binding (P = 0.0368);Loss of MoRF binding (P = 0.0368);Loss of MoRF binding (P = 0.0368);

MVP

0.43

MPC

0.40

ClinPred

0.084

GERP RS

2.2

Varity_R

0.093

gMVP

0.59

Mutation Taster

=99/1

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

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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