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GeneBe

3-152835843-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002563.5(P2RY1):ā€‹c.61C>Gā€‹(p.Pro21Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000059 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

P2RY1
NM_002563.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.456
Variant links:
Genes affected
P2RY1 (HGNC:8539): (purinergic receptor P2Y1) The product of this gene belongs to the family of 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 functions as a receptor for extracellular ATP and ADP. In platelets binding to ADP leads to mobilization of intracellular calcium ions via activation of phospholipase C, a change in platelet shape, and probably to platelet aggregation. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.027953148).
BS2
High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
P2RY1NM_002563.5 linkuse as main transcriptc.61C>G p.Pro21Ala missense_variant 1/1 ENST00000305097.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
P2RY1ENST00000305097.6 linkuse as main transcriptc.61C>G p.Pro21Ala missense_variant 1/1 NM_002563.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152226
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000800
AC:
2
AN:
250118
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135582
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00000886
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1460552
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
726602
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
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:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152344
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000642
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsApr 27, 2022The c.61C>G (p.P21A) alteration is located in exon 1 (coding exon 1) of the P2RY1 gene. This alteration results from a C to G substitution at nucleotide position 61, causing the proline (P) at amino acid position 21 to be replaced by an alanine (A). 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
0.063
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
15
DANN
Benign
0.77
DEOGEN2
Benign
0.20
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.37
N
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.028
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.23
N
REVEL
Benign
0.098
Sift
Benign
0.47
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.088
MutPred
0.39
Gain of catalytic residue at P21 (P = 0.0055);
MVP
0.32
MPC
0.50
ClinPred
0.97
D
GERP RS
1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.035
gMVP
0.12

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.

Other links and lift over

dbSNP: rs535974488; hg19: chr3-152553632; API