rs147189011

Variant names:

• chr11-73234243-C-A
• rs147189011
• NM_002564.4:c.84C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-73234243-C-A
• chr11-73234243-C-G
• chr11-73234243-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002564.4(P2RY2):​c.84C>A​(p.Asn28Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,614,182 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (1 hom.)
• Consequence: P2RY2 NM_002564.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.81
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017811626).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RY2	NM_002564.4	MANE Select	c.84C>A	p.Asn28Lys	missense	Exon 3 of 3	NP_002555.4
	P2RY2	NM_176071.3		c.84C>A	p.Asn28Lys	missense	Exon 3 of 3	NP_788085.3	P41231
	P2RY2	NM_176072.3		c.84C>A	p.Asn28Lys	missense	Exon 3 of 3	NP_788086.3	P41231

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RY2	ENST00000393597.7	TSL:1 MANE Select	c.84C>A	p.Asn28Lys	missense	Exon 3 of 3	ENSP00000377222.2	P41231
	P2RY2	ENST00000311131.6	TSL:1	c.84C>A	p.Asn28Lys	missense	Exon 3 of 3	ENSP00000310305.2	P41231
	P2RY2	ENST00000393596.2	TSL:1	c.84C>A	p.Asn28Lys	missense	Exon 3 of 3	ENSP00000377221.2	P41231

Frequencies

GnomAD3 genomes AF: 0.000703 AC: 107 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000386 AC: 97 AN: 251304 AF XY: 0.000353

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000361

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000276 AC: 403 AN: 1461880 Hom.: 1 Cov.: 29 AF XY: 0.000279 AC XY: 203 AN XY: 727246

African (AFR) AF: 0.00164 AC: 55 AN: 33480

American (AMR) AF: 0.00123 AC: 55 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000207 AC: 230 AN: 1112010

Other (OTH) AF: 0.000960 AC: 58 AN: 60396

GnomAD4 genome AF: 0.000716 AC: 109 AN: 152302 Hom.: 0 Cov.: 33 AF XY: 0.000752 AC XY: 56 AN XY: 74466

African (AFR) AF: 0.00103 AC: 43 AN: 41558

American (AMR) AF: 0.00216 AC: 33 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68028

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.000348 Hom.: 0

Bravo AF: 0.000929

ESP6500AA AF: 0.000682 AC: 3

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000288 AC: 35

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.9
DANN	Uncertain	0.97
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.8
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.040
Sift	Benign	0.13	T
Sift4G	Benign	0.33	T
Polyphen		0.037	B
Vest4		0.27
MutPred		0.52		Gain of methylation at N28 (P = 0.0182)
MVP		0.44
MPC		0.42
ClinPred		0.011	T
GERP RS		-0.98
Varity_R		0.093
gMVP		0.45
Mutation Taster		=73/27	polymorphism

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: rs147189011; hg19: chr11-72945288;