11-73234209-A-G

Position:

• chr11-73234209-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002564.4(P2RY2):​c.50A>G​(p.Asp17Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00592 in 1,613,886 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. D17D) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0055 (10 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (53 hom.)
• Consequence: P2RY2 NM_002564.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.439

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034140348).
• BP6: Variant 11-73234209-A-G is Benign according to our data. Variant chr11-73234209-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2642132.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RY2	NM_002564.4	c.50A>G	p.Asp17Gly	missense_variant	3/3	ENST00000393597.7
P2RY2	NM_176071.3	c.50A>G	p.Asp17Gly	missense_variant	3/3
P2RY2	NM_176072.3	c.50A>G	p.Asp17Gly	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RY2	ENST00000393597.7	c.50A>G	p.Asp17Gly	missense_variant	3/3	1	NM_002564.4	P1
P2RY2	ENST00000311131.6	c.50A>G	p.Asp17Gly	missense_variant	3/3	1		P1
P2RY2	ENST00000393596.2	c.50A>G	p.Asp17Gly	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.00550 AC: 836 AN: 152042 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.000870

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00699

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00791

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00519 AC: 1304 AN: 251038 Hom.: 7 AF XY: 0.00507 AC XY: 688 AN XY: 135656

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.0300

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00118

Gnomad FIN exome AF: 0.00680

Gnomad NFE exome AF: 0.00634

Gnomad OTH exome AF: 0.00522

GnomAD4 exome AF: 0.00596 AC: 8719 AN: 1461726 Hom.: 53 Cov.: 29 AF XY: 0.00597 AC XY: 4344 AN XY: 727170

Gnomad4 AFR exome AF: 0.000687

Gnomad4 AMR exome AF: 0.00177

Gnomad4 ASJ exome AF: 0.0298

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00147

Gnomad4 FIN exome AF: 0.00768

Gnomad4 NFE exome AF: 0.00620

Gnomad4 OTH exome AF: 0.00659

GnomAD4 genome AF: 0.00549 AC: 836 AN: 152160 Hom.: 10 Cov.: 33 AF XY: 0.00531 AC XY: 395 AN XY: 74400

Gnomad4 AFR AF: 0.000867

Gnomad4 AMR AF: 0.00347

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00699

Gnomad4 NFE AF: 0.00791

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00759 Hom.: 15

Bravo AF: 0.00468

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00804 AC: 69

ExAC AF: 0.00526 AC: 638

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

P2RY2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.049	T;T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.14	N
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.0034	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.28	N;N;N
REVEL	Benign	0.035
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.082	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.11
MVP		0.50
MPC		0.46
ClinPred		0.0056	T
GERP RS		1.0
Varity_R		0.071
gMVP		0.50

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: rs117372847; hg19: chr11-72945254;