11-73234975-C-T

Variant names:

• chr11-73234975-C-T
• rs1783596
• NM_002564.4:c.816C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002564.4(P2RY2):​c.816C>T​(p.Arg272Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,609,496 control chromosomes in the GnomAD database, including 245,662 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.56 (24286 hom., cov: 34)
  • Exomes 𝑓: 0.55 (221376 hom.)
• Consequence: P2RY2 NM_002564.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251
• Publications: 26 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-0.251 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RY2	NM_002564.4	c.816C>T	p.Arg272Arg	synonymous_variant	Exon 3 of 3	ENST00000393597.7	NP_002555.4
P2RY2	NM_176071.3	c.816C>T	p.Arg272Arg	synonymous_variant	Exon 3 of 3		NP_788085.3
P2RY2	NM_176072.3	c.816C>T	p.Arg272Arg	synonymous_variant	Exon 3 of 3		NP_788086.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RY2	ENST00000393597.7	c.816C>T	p.Arg272Arg	synonymous_variant	Exon 3 of 3	1	NM_002564.4	ENSP00000377222.2
P2RY2	ENST00000311131.6	c.816C>T	p.Arg272Arg	synonymous_variant	Exon 3 of 3	1		ENSP00000310305.2
P2RY2	ENST00000393596.2	c.816C>T	p.Arg272Arg	synonymous_variant	Exon 3 of 3	1		ENSP00000377221.2

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85783 AN: 152050 Hom.: 24266 Cov.: 34

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.584

GnomAD2 exomes AF: 0.566 AC: 140698 AN: 248494 AF XY: 0.558

Gnomad AFR exome AF: 0.565

Gnomad AMR exome AF: 0.657

Gnomad ASJ exome AF: 0.604

Gnomad EAS exome AF: 0.649

Gnomad FIN exome AF: 0.556

Gnomad NFE exome AF: 0.547

Gnomad OTH exome AF: 0.560

GnomAD4 exome AF: 0.550 AC: 800979 AN: 1457328 Hom.: 221376 Cov.: 61 AF XY: 0.547 AC XY: 397042 AN XY: 725204

African (AFR) AF: 0.571 AC: 19107 AN: 33474

American (AMR) AF: 0.654 AC: 29260 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 15522 AN: 26130

East Asian (EAS) AF: 0.621 AC: 24644 AN: 39696

South Asian (SAS) AF: 0.481 AC: 41461 AN: 86254

European-Finnish (FIN) AF: 0.554 AC: 27193 AN: 49062

Middle Eastern (MID) AF: 0.593 AC: 3420 AN: 5768

European-Non Finnish (NFE) AF: 0.546 AC: 606547 AN: 1111870

Other (OTH) AF: 0.560 AC: 33825 AN: 60358

GnomAD4 genome AF: 0.564 AC: 85861 AN: 152168 Hom.: 24286 Cov.: 34 AF XY: 0.563 AC XY: 41908 AN XY: 74400

African (AFR) AF: 0.568 AC: 23593 AN: 41514

American (AMR) AF: 0.636 AC: 9731 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2058 AN: 3472

East Asian (EAS) AF: 0.642 AC: 3320 AN: 5168

South Asian (SAS) AF: 0.481 AC: 2325 AN: 4830

European-Finnish (FIN) AF: 0.557 AC: 5904 AN: 10594

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37164 AN: 67984

Other (OTH) AF: 0.582 AC: 1225 AN: 2104

Alfa AF: 0.554 Hom.: 81707

Bravo AF: 0.575

Asia WGS AF: 0.559 AC: 1946 AN: 3478

EpiCase AF: 0.551

EpiControl AF: 0.550

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.2
DANN	Benign	0.85
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1783596; hg19: chr11-72946020; COSMIC: COSV60776158; COSMIC: COSV60776158;