11-73234826-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002564.4(P2RY2):ā€‹c.667C>Gā€‹(p.Arg223Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 34)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

P2RY2
NM_002564.4 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.538
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.818

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
P2RY2NM_002564.4 linkuse as main transcriptc.667C>G p.Arg223Gly missense_variant 3/3 ENST00000393597.7 NP_002555.4 P41231
P2RY2NM_176071.3 linkuse as main transcriptc.667C>G p.Arg223Gly missense_variant 3/3 NP_788085.3 P41231
P2RY2NM_176072.3 linkuse as main transcriptc.667C>G p.Arg223Gly missense_variant 3/3 NP_788086.3 P41231

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
P2RY2ENST00000393597.7 linkuse as main transcriptc.667C>G p.Arg223Gly missense_variant 3/31 NM_002564.4 ENSP00000377222.2 P41231
P2RY2ENST00000311131.6 linkuse as main transcriptc.667C>G p.Arg223Gly missense_variant 3/31 ENSP00000310305.2 P41231
P2RY2ENST00000393596.2 linkuse as main transcriptc.667C>G p.Arg223Gly missense_variant 3/31 ENSP00000377221.2 P41231

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD3 exomes
AF:
0.00000804
AC:
2
AN:
248668
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134690
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459122
Hom.:
0
Cov.:
56
AF XY:
0.00
AC XY:
0
AN XY:
725990
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34
ExAC
AF:
0.0000165
AC:
2

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 GeneticsDec 19, 2023The c.667C>G (p.R223G) alteration is located in exon 3 (coding exon 1) of the P2RY2 gene. This alteration results from a C to G substitution at nucleotide position 667, causing the arginine (R) at amino acid position 223 to be replaced by a glycine (G). 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
0.12
BayesDel_addAF
Benign
-0.092
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.46
T;T;T
Eigen
Benign
0.097
Eigen_PC
Benign
-0.082
FATHMM_MKL
Benign
0.33
N
LIST_S2
Uncertain
0.95
.;.;D
M_CAP
Uncertain
0.088
D
MetaRNN
Pathogenic
0.82
D;D;D
MetaSVM
Benign
-0.45
T
MutationAssessor
Uncertain
2.6
M;M;M
PrimateAI
Benign
0.45
T
PROVEAN
Pathogenic
-4.9
D;D;D
REVEL
Benign
0.28
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.0070
D;D;D
Polyphen
0.95
P;P;P
Vest4
0.66
MutPred
0.74
Loss of stability (P = 0.0158);Loss of stability (P = 0.0158);Loss of stability (P = 0.0158);
MVP
0.85
MPC
1.1
ClinPred
0.96
D
GERP RS
3.5
Varity_R
0.78
gMVP
0.73

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: rs774505848; hg19: chr11-72945871; API