NM_002564.4:c.442C>A

Variant names:

• chr11-73234601-C-A
• rs763479857
• NM_002564.4:c.442C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002564.4(P2RY2):​c.442C>A​(p.Arg148Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,414,620 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R148C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: P2RY2 NM_002564.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.442C>A	p.Arg148Ser	missense	Exon 3 of 3	NP_002555.4
	P2RY2	NM_176071.3		c.442C>A	p.Arg148Ser	missense	Exon 3 of 3	NP_788085.3	P41231
	P2RY2	NM_176072.3		c.442C>A	p.Arg148Ser	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.442C>A	p.Arg148Ser	missense	Exon 3 of 3	ENSP00000377222.2	P41231
	P2RY2	ENST00000311131.6	TSL:1	c.442C>A	p.Arg148Ser	missense	Exon 3 of 3	ENSP00000310305.2	P41231
	P2RY2	ENST00000393596.2	TSL:1	c.442C>A	p.Arg148Ser	missense	Exon 3 of 3	ENSP00000377221.2	P41231

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000283 AC: 4 AN: 1414620 Hom.: 0 Cov.: 57 AF XY: 0.00000287 AC XY: 2 AN XY: 697832

African (AFR) AF: 0.00 AC: 0 AN: 32458

American (AMR) AF: 0.00 AC: 0 AN: 40472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22620

East Asian (EAS) AF: 0.00 AC: 0 AN: 39294

South Asian (SAS) AF: 0.00 AC: 0 AN: 77438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5484

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1087598

Other (OTH) AF: 0.0000514 AC: 3 AN: 58388

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

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	0.12
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.26
Sift	Benign	0.053	T
Sift4G	Uncertain	0.030	D
Polyphen		0.69	P
Vest4		0.20
MutPred		0.66		Loss of methylation at R148 (P = 0.0167)
MVP		0.90
MPC		0.43
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.72
gMVP		0.64
Mutation Taster		=65/35	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: rs763479857; hg19: chr11-72945646;