rs75585377

Positions:

chr12-132619451-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_012226.5(P2RX2):c.118C>T(p.Arg40Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,612,196 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 9 hom., cov: 32)

Exomes 𝑓: 0.015 ( 147 hom. )

Consequence

P2RX2
NM_012226.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.180

Variant links:

Genes affected

P2RX2 (HGNC:15459): (purinergic receptor P2X 2) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel. Binding to ATP mediates synaptic transmission between neurons and from neurons to smooth muscle. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Aug 2013]

P2RX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-132619451-C-T is Benign according to our data. Variant chr12-132619451-C-T is described in ClinVar as [Benign]. Clinvar id is 226983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-132619451-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0149 (21786/1460106) while in subpopulation SAS AF= 0.0163 (1403/86248). AF 95% confidence interval is 0.0161. There are 147 homozygotes in gnomad4_exome. There are 10965 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1574 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX2	NM_170682.4 link	c.186C>T	p.Ile62Ile	synonymous_variant	2/11	ENST00000643471.2	NP_733782.1	Q9UBL9-1Q32MC3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX2	ENST00000643471.2 link	c.186C>T	p.Ile62Ile	synonymous_variant	2/11		NM_170682.4	ENSP00000494644.1		Q9UBL9-1

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1574

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00336

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.00661

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.0149

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0112

AC:

2778

AN:

248670

Hom.:

AF XY:

0.0120

AC XY:

1621

AN XY:

135026

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.00898

Gnomad ASJ exome

AF:

0.0200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0144

Gnomad FIN exome

AF:

0.00679

Gnomad NFE exome

AF:

0.0142

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.0149

AC:

21786

AN:

1460106

Hom.:

147

Cov.:

AF XY:

0.0151

AC XY:

10965

AN XY:

726432

show subpopulations

Gnomad4 AFR exome

AF:

0.00191

Gnomad4 AMR exome

AF:

0.00980

Gnomad4 ASJ exome

AF:

0.0207

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0163

Gnomad4 FIN exome

AF:

0.00761

Gnomad4 NFE exome

AF:

0.0163

Gnomad4 OTH exome

AF:

0.0132

GnomAD4 genome

AF:

0.0103

AC:

1574

AN:

152090

Hom.:

Cov.:

AF XY:

0.00990

AC XY:

736

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00335

Gnomad4 AMR

AF:

0.0124

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.0131

Gnomad4 FIN

AF:

0.00661

Gnomad4 NFE

AF:

0.0149

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0137

Hom.:

Bravo

AF:

0.0108

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0155

AC:

133

ExAC

AF:

0.0107

AC:

1302

Asia WGS

AF:

0.00607

AC:

AN:

3472

EpiCase

AF:

0.0181

EpiControl

AF:

0.0158

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	P2RX2: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Ile62Ile in exon 2 of P2RX2: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 1.5% (133/8600) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs75585377). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 02, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

P2RX2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0073

MetaSVM

Benign

-1.1

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Polyphen

0.82

Vest4

0.27

ClinPred

0.037

GERP RS

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: 7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over