Variant 12-132618878-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_170682.4(P2RX2):c.62G>A(p.Cys21Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00047 in 1,378,608 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00039 ( 1 hom., cov: 29)

Exomes 𝑓: 0.00048 ( 12 hom. )

Consequence

P2RX2
NM_170682.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.92

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071820617).

BP6

Variant 12-132618878-G-A is Benign according to our data. Variant chr12-132618878-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 737145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 59 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX2	NM_170682.4 linkuse as main transcript	c.62G>A	p.Cys21Tyr	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.62G>A	p.Cys21Tyr	missense_variant	1/11		NM_170682.4	ENSP00000494644	A2	Q9UBL9-1

Frequencies

GnomAD3 genomes

AF:

0.000386

AC:

AN:

150308

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:

0.0120

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00111

AC:

142

AN:

128490

Hom.:

AF XY:

0.00159

AC XY:

116

AN XY:

73002

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000134

Gnomad SAS exome

AF:

0.0104

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000847

GnomAD4 exome

AF:

0.000480

AC:

589

AN:

1228192

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

405

AN XY:

603610

show subpopulations

Gnomad4 AFR exome

AF:

0.0000796

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000101

Gnomad4 OTH exome

AF:

0.000581

GnomAD4 genome

AF:

0.000392

AC:

AN:

150416

Hom.:

Cov.:

AF XY:

0.000599

AC XY:

AN XY:

73474

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:

0.0122

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000693

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.00153

AC:

182

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 21, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 04, 2022	See Variant Classification Assertion Criteria. -

P2RX2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 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

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.59

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

Eigen

Benign

0.16

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.83

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

MetaRNN

Benign

0.0072

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M;M;M;M;M;M;M;.

MutationTaster

Benign

0.99

D;D;D;D;D;N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-4.1

.;D;D;D;D;D;D;D;.

REVEL

Benign

0.20

Sift

Benign

0.10

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

Sift4G

Uncertain

0.0060

.;D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;P;D;B;D;B;D;D

Vest4

0.51, 0.32, 0.61, 0.39, 0.57, 0.59, 0.56, 0.52

MutPred

0.57

Gain of MoRF binding (P = 0.0741);Gain of MoRF binding (P = 0.0741);Gain of MoRF binding (P = 0.0741);Gain of MoRF binding (P = 0.0741);Gain of MoRF binding (P = 0.0741);Gain of MoRF binding (P = 0.0741);Gain of MoRF binding (P = 0.0741);Gain of MoRF binding (P = 0.0741);Gain of MoRF binding (P = 0.0741);

MVP

0.48

MPC

2.4

ClinPred

0.24

GERP RS

4.1

Varity_R

0.37

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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