11-73234826-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_002564.4(P2RY2):āc.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
NM_002564.4 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 0.538
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 |
---|---|---|---|---|---|---|---|---|
P2RY2 | NM_002564.4 | c.667C>G | p.Arg223Gly | missense_variant | 3/3 | ENST00000393597.7 | NP_002555.4 | |
P2RY2 | NM_176071.3 | c.667C>G | p.Arg223Gly | missense_variant | 3/3 | NP_788085.3 | ||
P2RY2 | NM_176072.3 | c.667C>G | p.Arg223Gly | missense_variant | 3/3 | NP_788086.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
P2RY2 | ENST00000393597.7 | c.667C>G | p.Arg223Gly | missense_variant | 3/3 | 1 | NM_002564.4 | ENSP00000377222.2 | ||
P2RY2 | ENST00000311131.6 | c.667C>G | p.Arg223Gly | missense_variant | 3/3 | 1 | ENSP00000310305.2 | |||
P2RY2 | ENST00000393596.2 | c.667C>G | p.Arg223Gly | missense_variant | 3/3 | 1 | ENSP00000377221.2 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
Cov.:
34
GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248668Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134690
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459122Hom.: 0 Cov.: 56 AF XY: 0.00 AC XY: 0AN XY: 725990
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GnomAD4 genome Cov.: 34
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34
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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 | Dec 19, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
.;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;P;P
Vest4
MutPred
Loss of stability (P = 0.0158);Loss of stability (P = 0.0158);Loss of stability (P = 0.0158);
MVP
MPC
1.1
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at