12-132618872-G-A

Position:

chr12-132618872-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_170682.4(P2RX2):c.56G>A(p.Arg19Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,374,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000047 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

P2RX2
NM_170682.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.713

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07890704).

BP6

Variant 12-132618872-G-A is Benign according to our data. Variant chr12-132618872-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1195462.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX2	NM_170682.4 linkuse as main transcript	c.56G>A	p.Arg19Gln	missense_variant	1/11	ENST00000643471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX2	ENST00000643471.2 linkuse as main transcript	c.56G>A	p.Arg19Gln	missense_variant	1/11		NM_170682.4	A2	Q9UBL9-1

Frequencies

GnomAD3 genomes

AF:

0.0000466

AC:

AN:

150294

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000892

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

123956

Hom.:

AF XY:

0.0000283

AC XY:

AN XY:

70652

show subpopulations

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:

0.0000326

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000368

AC:

AN:

1224210

Hom.:

Cov.:

AF XY:

0.0000366

AC XY:

AN XY:

601514

show subpopulations

Gnomad4 AFR exome

AF:

0.0000400

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000210

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000425

Gnomad4 OTH exome

AF:

0.0000209

GnomAD4 genome

AF:

0.0000466

AC:

AN:

150294

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

73296

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000892

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.0000168

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.56G>A (p.R19Q) alteration is located in exon 1 (coding exon 1) of the P2RX2 gene. This alteration results from a G to A substitution at nucleotide position 56, causing the arginine (R) at amino acid position 19 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 05, 2019

In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27766948) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.084

T;T;.;.;.;.;.;.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.76

.;T;T;T;T;T;T;T;T

M_CAP

Pathogenic

0.50

MetaRNN

Benign

0.079

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.67

N;N;N;N;N;N;N;N;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.37

.;N;N;N;N;N;N;N;.

REVEL

Benign

0.026

Sift

Benign

0.28

.;T;T;T;T;T;T;T;.

Sift4G

Benign

0.59

.;T;T;T;T;T;T;T;T

Polyphen

0.033

B;B;B;B;B;B;B;B;B

Vest4

0.11, 0.22, 0.23, 0.17, 0.20, 0.20, 0.11

MVP

0.31

MPC

0.96

ClinPred

0.073

GERP RS

0.56

Varity_R

0.11

gMVP

0.16

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

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