rs4944831

Positions:

• chr11-73223683-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002564.4(P2RY2):​c.-199-4298G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,058 control chromosomes in the GnomAD database, including 52,945 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.83 (52945 hom., cov: 30)
• Consequence: P2RY2 NM_002564.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RY2	NM_002564.4	c.-199-4298G>T		intron_variant		ENST00000393597.7
P2RY2	NM_176071.3	c.-199-4298G>T		intron_variant
P2RY2	NM_176072.3	c.-333-4298G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RY2	ENST00000393597.7	c.-199-4298G>T		intron_variant		1	NM_002564.4	P1
P2RY2	ENST00000311131.6	c.-333-4298G>T		intron_variant		1		P1
P2RY2	ENST00000393596.2	c.-199-4298G>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126649 AN: 151940 Hom.: 52900 Cov.: 30

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.899

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.791

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.834 AC: 126755 AN: 152058 Hom.: 52945 Cov.: 30 AF XY: 0.840 AC XY: 62415 AN XY: 74344

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.899

Gnomad4 FIN AF: 0.926

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.792

Alfa AF: 0.836 Hom.: 37696

Bravo AF: 0.823

Asia WGS AF: 0.847 AC: 2944 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.81

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: rs4944831; hg19: chr11-72934728;