11-73234243-C-A

Position:

chr11-73234243-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002564.4(P2RY2):c.84C>A(p.Asn28Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,614,182 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 1 hom. )

Consequence

P2RY2
NM_002564.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.81

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017811626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RY2	NM_002564.4 linkuse as main transcript	c.84C>A	p.Asn28Lys	missense_variant	3/3	ENST00000393597.7	NP_002555.4	P41231
P2RY2	NM_176071.3 linkuse as main transcript	c.84C>A	p.Asn28Lys	missense_variant	3/3		NP_788085.3	P41231
P2RY2	NM_176072.3 linkuse as main transcript	c.84C>A	p.Asn28Lys	missense_variant	3/3		NP_788086.3	P41231

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
P2RY2	ENST00000393597.7 linkuse as main transcript	c.84C>A	p.Asn28Lys	missense_variant	3/3	1	NM_002564.4	ENSP00000377222.2	P41231
P2RY2	ENST00000311131.6 linkuse as main transcript	c.84C>A	p.Asn28Lys	missense_variant	3/3	1		ENSP00000310305.2	P41231
P2RY2	ENST00000393596.2 linkuse as main transcript	c.84C>A	p.Asn28Lys	missense_variant	3/3	1		ENSP00000377221.2	P41231

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000386

AC:

AN:

251304

Hom.:

AF XY:

0.000353

AC XY:

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000361

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000276

AC:

403

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000279

AC XY:

203

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000207

Gnomad4 OTH exome

AF:

0.000960

GnomAD4 genome

AF:

0.000716

AC:

109

AN:

152302

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000288

Hom.:

Bravo

AF:

0.000929

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000288

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000652

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 15, 2021

The c.84C>A (p.N28K) alteration is located in exon 3 (coding exon 1) of the P2RY2 gene. This alteration results from a C to A substitution at nucleotide position 84, causing the asparagine (N) at amino acid position 28 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.9

DANN

Uncertain

0.97

DEOGEN2

Benign

0.11

T;T;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.81

.;.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;L

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.040

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.037

B;B;B

Vest4

0.27

MutPred

0.52

Gain of methylation at N28 (P = 0.0182);Gain of methylation at N28 (P = 0.0182);Gain of methylation at N28 (P = 0.0182);

MVP

0.44

MPC

0.42

ClinPred

0.011

GERP RS

-0.98

Varity_R

0.093

gMVP

0.45

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over