11-73235095-G-C

Variant names:

• chr11-73235095-G-C
• rs3741156
• NM_002564.4:c.936G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002564.4(P2RY2):​c.936G>C​(p.Arg312Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,606,658 control chromosomes in the GnomAD database, including 54,113 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (4529 hom., cov: 33)
  • Exomes 𝑓: 0.25 (49584 hom.)
• Consequence: P2RY2 NM_002564.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 27 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.6395917E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RY2	NM_002564.4	c.936G>C	p.Arg312Ser	missense_variant	Exon 3 of 3	ENST00000393597.7	NP_002555.4
P2RY2	NM_176071.3	c.936G>C	p.Arg312Ser	missense_variant	Exon 3 of 3		NP_788085.3
P2RY2	NM_176072.3	c.936G>C	p.Arg312Ser	missense_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.936G>C	p.Arg312Ser	missense_variant	Exon 3 of 3	1	NM_002564.4	ENSP00000377222.2
P2RY2	ENST00000311131.6	c.936G>C	p.Arg312Ser	missense_variant	Exon 3 of 3	1		ENSP00000310305.2
P2RY2	ENST00000393596.2	c.936G>C	p.Arg312Ser	missense_variant	Exon 3 of 3	1		ENSP00000377221.2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32109 AN: 152124 Hom.: 4516 Cov.: 33

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.219

GnomAD2 exomes AF: 0.286 AC: 69849 AN: 244360 AF XY: 0.277

Gnomad AFR exome AF: 0.0499

Gnomad AMR exome AF: 0.467

Gnomad ASJ exome AF: 0.174

Gnomad EAS exome AF: 0.566

Gnomad FIN exome AF: 0.262

Gnomad NFE exome AF: 0.241

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.250 AC: 363374 AN: 1454416 Hom.: 49584 Cov.: 51 AF XY: 0.249 AC XY: 180098 AN XY: 723668

African (AFR) AF: 0.0420 AC: 1405 AN: 33460

American (AMR) AF: 0.455 AC: 20265 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4352 AN: 26022

East Asian (EAS) AF: 0.543 AC: 21527 AN: 39666

South Asian (SAS) AF: 0.256 AC: 22025 AN: 86144

European-Finnish (FIN) AF: 0.258 AC: 12345 AN: 47822

Middle Eastern (MID) AF: 0.142 AC: 817 AN: 5758

European-Non Finnish (NFE) AF: 0.239 AC: 265833 AN: 1110704

Other (OTH) AF: 0.246 AC: 14805 AN: 60256

GnomAD4 genome AF: 0.211 AC: 32135 AN: 152242 Hom.: 4529 Cov.: 33 AF XY: 0.216 AC XY: 16098 AN XY: 74418

African (AFR) AF: 0.0523 AC: 2175 AN: 41570

American (AMR) AF: 0.355 AC: 5435 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 581 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2871 AN: 5162

South Asian (SAS) AF: 0.271 AC: 1309 AN: 4832

European-Finnish (FIN) AF: 0.253 AC: 2674 AN: 10590

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16375 AN: 68010

Other (OTH) AF: 0.222 AC: 468 AN: 2110

Alfa AF: 0.222 Hom.: 1037

Bravo AF: 0.215

TwinsUK AF: 0.235 AC: 871

ALSPAC AF: 0.238 AC: 919

ESP6500AA AF: 0.0593 AC: 261

ESP6500EA AF: 0.237 AC: 2036

ExAC AF: 0.272 AC: 32959

Asia WGS AF: 0.381 AC: 1323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.049	T;T;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.75	.;.;T
MetaRNN	Benign	0.00026	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L;L;L
PhyloP100		2.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.52	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.095	T;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.015	B;B;B
Vest4		0.23
MutPred		0.45		Loss of MoRF binding (P = 0.0368);Loss of MoRF binding (P = 0.0368);Loss of MoRF binding (P = 0.0368);
MPC		0.40
ClinPred		0.0021	T
GERP RS		2.2
Varity_R		0.093
gMVP		0.59
Mutation Taster		=99/1	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: rs3741156; hg19: chr11-72946140; COSMIC: COSV60775453; COSMIC: COSV60775453;