11-73235112-G-T

Variant names:

• chr11-73235112-G-T
• rs759366933
• NM_002564.4:c.953G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002564.4(P2RY2):​c.953G>T​(p.Arg318Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. R318G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: P2RY2 NM_002564.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.70
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1819433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RY2	NM_002564.4	c.953G>T	p.Arg318Leu	missense_variant	Exon 3 of 3	ENST00000393597.7	NP_002555.4
P2RY2	NM_176071.3	c.953G>T	p.Arg318Leu	missense_variant	Exon 3 of 3		NP_788085.3
P2RY2	NM_176072.3	c.953G>T	p.Arg318Leu	missense_variant	Exon 3 of 3		NP_788086.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RY2	ENST00000393597.7	c.953G>T	p.Arg318Leu	missense_variant	Exon 3 of 3	1	NM_002564.4	ENSP00000377222.2
P2RY2	ENST00000311131.6	c.953G>T	p.Arg318Leu	missense_variant	Exon 3 of 3	1		ENSP00000310305.2
P2RY2	ENST00000393596.2	c.953G>T	p.Arg318Leu	missense_variant	Exon 3 of 3	1		ENSP00000377221.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.79	.;.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L;L
PhyloP100		2.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.021	D;D;D
Polyphen		0.011	B;B;B
Vest4		0.49
MutPred		0.47		Loss of MoRF binding (P = 0.0269);Loss of MoRF binding (P = 0.0269);Loss of MoRF binding (P = 0.0269);
MVP		0.47
MPC		0.44
ClinPred		0.44	T
GERP RS		3.3
Varity_R		0.14
gMVP		0.58
Mutation Taster		=88/12	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: rs759366933; hg19: chr11-72946157;