rs1626154

chr11-73235159-C-Achr11-73235159-C-Gchr11-73235159-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002564.4(P2RY2):c.1000C>A(p.Arg334Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R334C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: P2RY2 NM_002564.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14327392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RY2	NM_002564.4	c.1000C>A	p.Arg334Ser	missense_variant	3/3	ENST00000393597.7
P2RY2	NM_176071.3	c.1000C>A	p.Arg334Ser	missense_variant	3/3
P2RY2	NM_176072.3	c.1000C>A	p.Arg334Ser	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RY2	ENST00000393597.7	c.1000C>A	p.Arg334Ser	missense_variant	3/3	1	NM_002564.4	P1
P2RY2	ENST00000311131.6	c.1000C>A	p.Arg334Ser	missense_variant	3/3	1		P1
P2RY2	ENST00000393596.2	c.1000C>A	p.Arg334Ser	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000411 AC: 1 AN: 243224 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 132328

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456242 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 724532

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	15
Dann	Uncertain	0.98
DEOGEN2	Benign	0.046	T;T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.31	N
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L;L
MutationTaster	Benign	0.95	P;P;P
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.070	N;N;N
REVEL	Benign	0.056
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.36	B;B;B
Vest4		0.19
MutPred		0.33		Gain of phosphorylation at R334 (P = 0.0056);Gain of phosphorylation at R334 (P = 0.0056);Gain of phosphorylation at R334 (P = 0.0056);
MVP		0.49
MPC		0.40
ClinPred		0.20	T
GERP RS		3.4
Varity_R		0.13
gMVP		0.51

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: rs1626154; hg19: chr11-72946204;