Genetic Variant P2RY2:p.Pro46Leu (chr11-73234296-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002564.4(P2RY2):c.137C>T(p.Pro46Leu) variant causes a missense change. The variant allele was found at a frequency of 0.926 in 1,614,140 control chromosomes in the GnomAD database, including 693,023 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.92 ( 64724 hom., cov: 33)

Exomes 𝑓: 0.93 ( 628299 hom. )

Consequence

P2RY2
NM_002564.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.24

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.1374424E-6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RY2	NM_002564.4 link	c.137C>T	p.Pro46Leu	missense_variant	Exon 3 of 3	ENST00000393597.7	NP_002555.4	P41231
P2RY2	NM_176071.3 link	c.137C>T	p.Pro46Leu	missense_variant	Exon 3 of 3		NP_788085.3	P41231
P2RY2	NM_176072.3 link	c.137C>T	p.Pro46Leu	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.137C>T	p.Pro46Leu	missense_variant	Exon 3 of 3	1	NM_002564.4	ENSP00000377222.2	P41231
P2RY2	ENST00000311131.6 link	c.137C>T	p.Pro46Leu	missense_variant	Exon 3 of 3	1		ENSP00000310305.2	P41231
P2RY2	ENST00000393596.2 link	c.137C>T	p.Pro46Leu	missense_variant	Exon 3 of 3	1		ENSP00000377221.2	P41231

Frequencies

GnomAD3 genomes

AF:

0.922

AC:

140240

AN:

152156

Hom.:

64679

Cov.:

show subpopulations

Gnomad AFR

AF:

0.908

Gnomad AMI

AF:

0.977

Gnomad AMR

AF:

0.948

Gnomad ASJ

AF:

0.956

Gnomad EAS

AF:

0.894

Gnomad SAS

AF:

0.896

Gnomad FIN

AF:

0.921

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.926

Gnomad OTH

AF:

0.932

GnomAD3 exomes

AF:

0.926

AC:

232472

AN:

251108

Hom.:

107762

AF XY:

0.924

AC XY:

125392

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.909

Gnomad AMR exome

AF:

0.967

Gnomad ASJ exome

AF:

0.955

Gnomad EAS exome

AF:

0.886

Gnomad SAS exome

AF:

0.899

Gnomad FIN exome

AF:

0.920

Gnomad NFE exome

AF:

0.928

Gnomad OTH exome

AF:

0.930

GnomAD4 exome

AF:

0.927

AC:

1355002

AN:

1461866

Hom.:

628299

Cov.:

AF XY:

0.926

AC XY:

673478

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.906

Gnomad4 AMR exome

AF:

0.966

Gnomad4 ASJ exome

AF:

0.956

Gnomad4 EAS exome

AF:

0.894

Gnomad4 SAS exome

AF:

0.899

Gnomad4 FIN exome

AF:

0.922

Gnomad4 NFE exome

AF:

0.929

Gnomad4 OTH exome

AF:

0.926

GnomAD4 genome

AF:

0.922

AC:

140342

AN:

152274

Hom.:

64724

Cov.:

AF XY:

0.922

AC XY:

68644

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.908

Gnomad4 AMR

AF:

0.948

Gnomad4 ASJ

AF:

0.956

Gnomad4 EAS

AF:

0.894

Gnomad4 SAS

AF:

0.894

Gnomad4 FIN

AF:

0.921

Gnomad4 NFE

AF:

0.926

Gnomad4 OTH

AF:

0.933

Alfa

AF:

0.929

Hom.:

133605

Bravo

AF:

0.925

TwinsUK

AF:

0.930

AC:

3448

ALSPAC

AF:

0.925

AC:

3566

ESP6500AA

AF:

0.908

AC:

3997

ESP6500EA

AF:

0.926

AC:

7953

ExAC

AF:

0.922

AC:

111951

Asia WGS

AF:

0.891

AC:

3095

AN:

3476

EpiCase

AF:

0.931

EpiControl

AF:

0.929

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.022

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.047

T;T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.11

.;.;T

MetaRNN

Benign

0.0000021

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.7

N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

4.7

N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.027

MPC

0.35

ClinPred

0.0042

GERP RS

5.3

Varity_R

0.039

gMVP

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over