11-73234296-C-T

Variant names:

• chr11-73234296-C-T
• rs2511241
• NM_002564.4:c.137C>T

Variant summary

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

The NM_002564.4(P2RY2):​c.137C>T​(p.Pro46Leu) variant causes a missense change. The variant allele was found at a frequency of 0.926 in 1,614,140 control chromosomes in the GnomAD database, including 693,023 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 0.92 (64724 hom., cov: 33)
  • Exomes 𝑓: 0.93 (628299 hom.)
• Consequence: P2RY2 NM_002564.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.24
• Publications: 41 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=2.1374424E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002564.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RY2	NM_002564.4	MANE Select	c.137C>T	p.Pro46Leu	missense	Exon 3 of 3	NP_002555.4
	P2RY2	NM_176071.3		c.137C>T	p.Pro46Leu	missense	Exon 3 of 3	NP_788085.3
	P2RY2	NM_176072.3		c.137C>T	p.Pro46Leu	missense	Exon 3 of 3	NP_788086.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RY2	ENST00000393597.7	TSL:1 MANE Select	c.137C>T	p.Pro46Leu	missense	Exon 3 of 3	ENSP00000377222.2
	P2RY2	ENST00000311131.6	TSL:1	c.137C>T	p.Pro46Leu	missense	Exon 3 of 3	ENSP00000310305.2
	P2RY2	ENST00000393596.2	TSL:1	c.137C>T	p.Pro46Leu	missense	Exon 3 of 3	ENSP00000377221.2

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140240 AN: 152156 Hom.: 64679 Cov.: 33

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.932

GnomAD2 exomes AF: 0.926 AC: 232472 AN: 251108 AF XY: 0.924

Gnomad AFR exome AF: 0.909

Gnomad AMR exome AF: 0.967

Gnomad ASJ exome AF: 0.955

Gnomad EAS exome AF: 0.886

Gnomad FIN exome AF: 0.920

Gnomad NFE exome AF: 0.928

Gnomad OTH exome AF: 0.930

GnomAD4 exome AF: 0.927 AC: 1355002 AN: 1461866 Hom.: 628299 Cov.: 70 AF XY: 0.926 AC XY: 673478 AN XY: 727240

African (AFR) AF: 0.906 AC: 30321 AN: 33478

American (AMR) AF: 0.966 AC: 43190 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 24976 AN: 26134

East Asian (EAS) AF: 0.894 AC: 35504 AN: 39700

South Asian (SAS) AF: 0.899 AC: 77570 AN: 86256

European-Finnish (FIN) AF: 0.922 AC: 49221 AN: 53412

Middle Eastern (MID) AF: 0.909 AC: 5241 AN: 5768

European-Non Finnish (NFE) AF: 0.929 AC: 1033031 AN: 1112002

Other (OTH) AF: 0.926 AC: 55948 AN: 60396

GnomAD4 genome AF: 0.922 AC: 140342 AN: 152274 Hom.: 64724 Cov.: 33 AF XY: 0.922 AC XY: 68644 AN XY: 74436

African (AFR) AF: 0.908 AC: 37713 AN: 41540

American (AMR) AF: 0.948 AC: 14509 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 3320 AN: 3472

East Asian (EAS) AF: 0.894 AC: 4630 AN: 5180

South Asian (SAS) AF: 0.894 AC: 4314 AN: 4824

European-Finnish (FIN) AF: 0.921 AC: 9772 AN: 10614

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.926 AC: 62958 AN: 68024

Other (OTH) AF: 0.933 AC: 1973 AN: 2114

Alfa AF: 0.927 Hom.: 252265

Bravo AF: 0.925

TwinsUK AF: 0.930 AC: 3448

ALSPAC AF: 0.925 AC: 3566

ESP6500AA AF: 0.908 AC: 3997

ESP6500EA AF: 0.926 AC: 7953

ExAC AF: 0.922 AC: 111951

Asia WGS AF: 0.891 AC: 3095 AN: 3476

EpiCase AF: 0.931

EpiControl AF: 0.929

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.022
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.11	T
MetaRNN	Benign	0.0000021	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.7	N
PhyloP100		6.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	4.7	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.027
MPC		0.35
ClinPred		0.0042	T
GERP RS		5.3
Varity_R		0.039
gMVP		0.29
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: rs2511241; hg19: chr11-72945341; COSMIC: COSV60777289; COSMIC: COSV60777289;