Variant chr12-132618874-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_170682.4(P2RX2):c.58G>A(p.Gly20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000312 in 1,377,050 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

P2RX2
NM_170682.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.363

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2276977).

BS2

High AC in GnomAdExome4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX2	NM_170682.4 linkuse as main transcript	c.58G>A	p.Gly20Ser	missense_variant	1/11	ENST00000643471.2	NP_733782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX2	ENST00000643471.2 linkuse as main transcript	c.58G>A	p.Gly20Ser	missense_variant	1/11		NM_170682.4	ENSP00000494644	A2	Q9UBL9-1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150380

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000334

AC:

AN:

1226670

Hom.:

Cov.:

AF XY:

0.0000332

AC XY:

AN XY:

602848

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150380

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73372

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000297

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

May 06, 2022

In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

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

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.75

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

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.23

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;L;L;L;L;L;L;.

MutationTaster

Benign

0.99

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

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.6

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

REVEL

Benign

0.017

Sift

Uncertain

0.020

.;D;D;T;D;D;D;D;.

Sift4G

Benign

0.10

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

Polyphen

0.44

B;B;B;P;B;B;B;B;B

Vest4

0.16, 0.23, 0.18, 0.11, 0.20, 0.19, 0.12

MutPred

0.45

Gain of glycosylation at G20 (P = 0.024);Gain of glycosylation at G20 (P = 0.024);Gain of glycosylation at G20 (P = 0.024);Gain of glycosylation at G20 (P = 0.024);Gain of glycosylation at G20 (P = 0.024);Gain of glycosylation at G20 (P = 0.024);Gain of glycosylation at G20 (P = 0.024);Gain of glycosylation at G20 (P = 0.024);Gain of glycosylation at G20 (P = 0.024);

MVP

0.31

MPC

0.98

ClinPred

0.28

GERP RS

0.59

Varity_R

0.11

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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