11-73235095-G-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -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

GnomAD3 exomes AF: 0.286 AC: 69849 AN: 244360 Hom.: 12182 AF XY: 0.277 AC XY: 36682 AN XY: 132614

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 SAS exome AF: 0.258

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

Gnomad4 AFR exome AF: 0.0420

Gnomad4 AMR exome AF: 0.455

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.543

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.246

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

Gnomad4 AFR AF: 0.0523

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.222

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
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

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

Other links and lift over

dbSNP: rs3741156; hg19: chr11-72946140; COSMIC: COSV60775453; COSMIC: COSV60775453;