Genetic Variant P2RY2:p.Arg334Cys (chr11-73235159-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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: 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

Publications

28 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
P2RY2	NM_002564.4 link	c.1000C>T	p.Arg334Cys	missense_variant	Exon 3 of 3	ENST00000393597.7	NP_002555.4	P41231
P2RY2	NM_176071.3 link	c.1000C>T	p.Arg334Cys	missense_variant	Exon 3 of 3		NP_788085.3	P41231
P2RY2	NM_176072.3 link	c.1000C>T	p.Arg334Cys	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.1000C>T	p.Arg334Cys	missense_variant	Exon 3 of 3	1	NM_002564.4	ENSP00000377222.2	P41231
P2RY2	ENST00000311131.6 link	c.1000C>T	p.Arg334Cys	missense_variant	Exon 3 of 3	1		ENSP00000310305.2	P41231
P2RY2	ENST00000393596.2 link	c.1000C>T	p.Arg334Cys	missense_variant	Exon 3 of 3	1		ENSP00000377221.2	P41231

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

GnomAD2 exomes

AF:

0.152

AC:

37033

AN:

243224

AF XY:

0.154

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 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

African (AFR)

AF:

0.0342

AC:

1144

AN:

33466

American (AMR)

AF:

0.124

AC:

5515

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

7448

AN:

26060

East Asian (EAS)

AF:

0.0653

AC:

2590

AN:

39672

South Asian (SAS)

AF:

0.0748

AC:

6447

AN:

86142

European-Finnish (FIN)

AF:

0.236

AC:

11576

AN:

48964

Middle Eastern (MID)

AF:

0.272

AC:

1568

AN:

5760

European-Non Finnish (NFE)

AF:

0.188

AC:

208997

AN:

1111126

Other (OTH)

AF:

0.178

AC:

10757

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

12496

24993

37489

49986

62482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7218

14436

21654

28872

36090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.141

AC:

21426

AN:

152232

Hom.:

1988

Cov.:

AF XY:

0.142

AC XY:

10550

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0361

AC:

1502

AN:

41554

American (AMR)

AF:

0.167

AC:

2551

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

1009

AN:

3472

East Asian (EAS)

AF:

0.0596

AC:

308

AN:

5170

South Asian (SAS)

AF:

0.0692

AC:

334

AN:

4824

European-Finnish (FIN)

AF:

0.241

AC:

2558

AN:

10598

Middle Eastern (MID)

AF:

0.291

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.185

AC:

12571

AN:

68004

Other (OTH)

AF:

0.188

AC:

398

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

986

1972

2959

3945

4931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.174

Hom.:

6593

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

(source)

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

LIST_S2

Benign

0.66

.;.;T

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L

PhyloP100

1.7

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

Mutation Taster

=98/2

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over