11-73234586-C-T

Variant names:

• chr11-73234586-C-T
• rs776830259
• NM_002564.4:c.427C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002564.4(P2RY2):​c.427C>T​(p.Arg143Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000445 in 1,573,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: P2RY2 NM_002564.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.338
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3708918).

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.427C>T	p.Arg143Cys	missense	Exon 3 of 3	NP_002555.4
	P2RY2	NM_176071.3		c.427C>T	p.Arg143Cys	missense	Exon 3 of 3	NP_788085.3	P41231
	P2RY2	NM_176072.3		c.427C>T	p.Arg143Cys	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.427C>T	p.Arg143Cys	missense	Exon 3 of 3	ENSP00000377222.2	P41231
	P2RY2	ENST00000311131.6	TSL:1	c.427C>T	p.Arg143Cys	missense	Exon 3 of 3	ENSP00000310305.2	P41231
	P2RY2	ENST00000393596.2	TSL:1	c.427C>T	p.Arg143Cys	missense	Exon 3 of 3	ENSP00000377221.2	P41231

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152250 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000422 AC: 6 AN: 1421108 Hom.: 0 Cov.: 56 AF XY: 0.00000142 AC XY: 1 AN XY: 701786

African (AFR) AF: 0.00 AC: 0 AN: 32624

American (AMR) AF: 0.00 AC: 0 AN: 41420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39362

South Asian (SAS) AF: 0.00 AC: 0 AN: 78208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5518

European-Non Finnish (NFE) AF: 0.00000550 AC: 6 AN: 1090922

Other (OTH) AF: 0.00 AC: 0 AN: 58668

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152250 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68052

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.34
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.27
Sift	Benign	0.036	D
Sift4G	Benign	0.073	T
Polyphen		0.99	D
Vest4		0.32
MutPred		0.59		Gain of catalytic residue at W144 (P = 5e-04)
MVP		0.75
MPC		0.50
ClinPred		0.86	D
GERP RS		4.5
Varity_R		0.18
gMVP		0.34
Mutation Taster		=79/21	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: rs776830259; hg19: chr11-72945631;