Variant rs144300117 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 ENST00000449132.6(P2RX2):c.655G>A(p.Ala219Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000794 in 1,613,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

P2RX2
ENST00000449132.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.320

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.037946165).

BP6

Variant 12-132620571-G-A is Benign according to our data. Variant chr12-132620571-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-132620571-G-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX2	NM_170682.4 linkuse as main transcript	c.762G>A	p.Glu254=	synonymous_variant	7/11	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.762G>A	p.Glu254=	synonymous_variant	7/11		NM_170682.4	ENSP00000494644	A2	Q9UBL9-1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000840

AC:

AN:

250086

Hom.:

AF XY:

0.0000887

AC XY:

AN XY:

135306

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

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:

0.000167

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000815

AC:

119

AN:

1460860

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.000103

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000151

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jul 08, 2015

Glu254Glu in exon 7 of P2RX2: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 7/65936 European chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs144300117). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 19, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.0

DANN

Benign

0.75

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.24

M_CAP

Benign

0.0080

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

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

PROVEAN

Benign

0.32

REVEL

Benign

0.081

Sift

Benign

0.84

Sift4G

Benign

0.63

Polyphen

0.0010

Vest4

0.29

MVP

0.099

ClinPred

0.011

GERP RS

1.5

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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