chr11-73235099-G-A

Position:

chr11-73235099-G-A

Variant summary

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

The NM_002564.4(P2RY2):c.940G>A(p.Val314Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000286 in 1,606,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

P2RY2
NM_002564.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

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:

Genome browser will be placed here

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=0.063801855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
P2RY2	NM_002564.4 linkuse as main transcript	c.940G>A	p.Val314Ile	missense_variant	3/3	ENST00000393597.7
P2RY2	NM_176071.3 linkuse as main transcript	c.940G>A	p.Val314Ile	missense_variant	3/3
P2RY2	NM_176072.3 linkuse as main transcript	c.940G>A	p.Val314Ile	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
P2RY2	ENST00000393597.7 linkuse as main transcript	c.940G>A	p.Val314Ile	missense_variant	3/3	1	NM_002564.4	P1
P2RY2	ENST00000311131.6 linkuse as main transcript	c.940G>A	p.Val314Ile	missense_variant	3/3	1		P1
P2RY2	ENST00000393596.2 linkuse as main transcript	c.940G>A	p.Val314Ile	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000536

AC:

AN:

242428

Hom.:

AF XY:

0.0000607

AC XY:

AN XY:

131772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000656

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000234

AC:

AN:

1453754

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

723320

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000480

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000577

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Mar 06, 2023

The c.940G>A (p.V314I) alteration is located in exon 3 (coding exon 1) of the P2RY2 gene. This alteration results from a G to A substitution at nucleotide position 940, causing the valine (V) at amino acid position 314 to be replaced by an isoleucine (I). 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

0.17

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.067

T;T;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.68

.;.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.064

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.14

N;N;N

REVEL

Benign

0.060

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.40

T;T;T

Polyphen

0.89

P;P;P

Vest4

0.26

MutPred

0.51

Loss of MoRF binding (P = 0.1175);Loss of MoRF binding (P = 0.1175);Loss of MoRF binding (P = 0.1175);

MVP

0.46

MPC

0.34

ClinPred

0.048

GERP RS

3.6

Varity_R

0.027

gMVP

0.30

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