Variant 11-73234508-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002564.4(P2RY2):c.349C>A(p.Leu117Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,856 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

P2RY2
NM_002564.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
P2RY2	NM_002564.4 linkuse as main transcript	c.349C>A	p.Leu117Ile	missense_variant	3/3	ENST00000393597.7
P2RY2	NM_176071.3 linkuse as main transcript	c.349C>A	p.Leu117Ile	missense_variant	3/3
P2RY2	NM_176072.3 linkuse as main transcript	c.349C>A	p.Leu117Ile	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
P2RY2	ENST00000393597.7 linkuse as main transcript	c.349C>A	p.Leu117Ile	missense_variant	3/3	1	NM_002564.4	P1
P2RY2	ENST00000311131.6 linkuse as main transcript	c.349C>A	p.Leu117Ile	missense_variant	3/3	1		P1
P2RY2	ENST00000393596.2 linkuse as main transcript	c.349C>A	p.Leu117Ile	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250324

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135258

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460856

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726626

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000959

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

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

Jan 23, 2024

The c.349C>A (p.L117I) 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 349, causing the leucine (L) at amino acid position 117 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

Pathogenic

0.66

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.55

D;D;D

MetaSVM

Uncertain

-0.11

MutationAssessor

Benign

1.9

L;L;L

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.9

N;N;N

REVEL

Uncertain

0.43

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.52

MutPred

0.60

Gain of catalytic residue at L117 (P = 0.0071);Gain of catalytic residue at L117 (P = 0.0071);Gain of catalytic residue at L117 (P = 0.0071);

MVP

0.91

MPC

1.2

ClinPred

0.80

GERP RS

5.3

Varity_R

0.56

gMVP

0.35

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