11-73234379-C-T

Variant summary

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

The NM_002564.4(P2RY2):​c.220C>T​(p.His74Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,242 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

P2RY2
NM_002564.4 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17
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]

Genome browser will be placed here

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 rank MANE Protein UniProt
P2RY2NM_002564.4 linkc.220C>T p.His74Tyr missense_variant Exon 3 of 3 ENST00000393597.7 NP_002555.4 P41231
P2RY2NM_176071.3 linkc.220C>T p.His74Tyr missense_variant Exon 3 of 3 NP_788085.3 P41231
P2RY2NM_176072.3 linkc.220C>T p.His74Tyr missense_variant Exon 3 of 3 NP_788086.3 P41231

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
P2RY2ENST00000393597.7 linkc.220C>T p.His74Tyr missense_variant Exon 3 of 3 1 NM_002564.4 ENSP00000377222.2 P41231
P2RY2ENST00000311131.6 linkc.220C>T p.His74Tyr missense_variant Exon 3 of 3 1 ENSP00000310305.2 P41231
P2RY2ENST00000393596.2 linkc.220C>T p.His74Tyr missense_variant Exon 3 of 3 1 ENSP00000377221.2 P41231

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152236
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00000796
AC:
2
AN:
251150
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.000123
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461888
Hom.:
0
Cov.:
56
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152354
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
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:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 22, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.220C>T (p.H74Y) alteration is located in exon 3 (coding exon 1) of the P2RY2 gene. This alteration results from a C to T substitution at nucleotide position 220, causing the histidine (H) at amino acid position 74 to be replaced by a tyrosine (Y). 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
0.75
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.28
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.40
T;T;T
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Pathogenic
0.98
.;.;D
M_CAP
Benign
0.036
D
MetaRNN
Uncertain
0.67
D;D;D
MetaSVM
Benign
-0.30
T
MutationAssessor
Uncertain
2.4
M;M;M
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-3.7
D;D;D
REVEL
Uncertain
0.29
Sift
Uncertain
0.0050
D;D;D
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.57
MutPred
0.79
Loss of glycosylation at T69 (P = 0.2247);Loss of glycosylation at T69 (P = 0.2247);Loss of glycosylation at T69 (P = 0.2247);
MVP
0.85
MPC
1.2
ClinPred
0.96
D
GERP RS
4.2
Varity_R
0.80
gMVP
0.74

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: rs557094128; hg19: chr11-72945424; COSMIC: COSV105137134; COSMIC: COSV105137134; API