Variant 11-73235159-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002564.4(P2RY2):c.1000C>T(p.Arg334Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,608,334 control chromosomes in the GnomAD database, including 26,288 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.14 ( 1988 hom., cov: 33)

Exomes 𝑓: 0.18 ( 24300 hom. )

Consequence

P2RY2
NM_002564.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

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=0.004827827).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
P2RY2	NM_002564.4 linkuse as main transcript	c.1000C>T	p.Arg334Cys	missense_variant	3/3	ENST00000393597.7
P2RY2	NM_176071.3 linkuse as main transcript	c.1000C>T	p.Arg334Cys	missense_variant	3/3
P2RY2	NM_176072.3 linkuse as main transcript	c.1000C>T	p.Arg334Cys	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
P2RY2	ENST00000393597.7 linkuse as main transcript	c.1000C>T	p.Arg334Cys	missense_variant	3/3	1	NM_002564.4	P1
P2RY2	ENST00000311131.6 linkuse as main transcript	c.1000C>T	p.Arg334Cys	missense_variant	3/3	1		P1
P2RY2	ENST00000393596.2 linkuse as main transcript	c.1000C>T	p.Arg334Cys	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21432

AN:

152116

Hom.:

1991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0361

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.0596

Gnomad SAS

AF:

0.0694

Gnomad FIN

AF:

0.241

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.190

GnomAD3 exomes

AF:

0.152

AC:

37033

AN:

243224

Hom.:

3480

AF XY:

0.154

AC XY:

20407

AN XY:

132328

show subpopulations

Gnomad AFR exome

AF:

0.0344

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.0553

Gnomad SAS exome

AF:

0.0714

Gnomad FIN exome

AF:

0.248

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.189

GnomAD4 exome

AF:

0.176

AC:

256042

AN:

1456102

Hom.:

24300

Cov.:

AF XY:

0.174

AC XY:

126289

AN XY:

724460

show subpopulations

Gnomad4 AFR exome

AF:

0.0342

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.286

Gnomad4 EAS exome

AF:

0.0653

Gnomad4 SAS exome

AF:

0.0748

Gnomad4 FIN exome

AF:

0.236

Gnomad4 NFE exome

AF:

0.188

Gnomad4 OTH exome

AF:

0.178

GnomAD4 genome

AF:

0.141

AC:

21426

AN:

152232

Hom.:

1988

Cov.:

AF XY:

0.142

AC XY:

10550

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0361

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.291

Gnomad4 EAS

AF:

0.0596

Gnomad4 SAS

AF:

0.0692

Gnomad4 FIN

AF:

0.241

Gnomad4 NFE

AF:

0.185

Gnomad4 OTH

AF:

0.188

Alfa

AF:

0.183

Hom.:

5207

Bravo

AF:

0.135

TwinsUK

AF:

0.184

AC:

684

ALSPAC

AF:

0.190

AC:

731

ESP6500AA

AF:

0.0405

AC:

178

ESP6500EA

AF:

0.186

AC:

1595

ExAC

AF:

0.148

AC:

17981

Asia WGS

AF:

0.0770

AC:

268

AN:

3478

EpiCase

AF:

0.201

EpiControl

AF:

0.202

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.33

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L

MutationTaster

Benign

0.055

P;P;P

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.070

Sift

Uncertain

0.026

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.11

MPC

0.87

ClinPred

0.0098

GERP RS

3.4

Varity_R

0.11

gMVP

0.51

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