Variant 12-132618825-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_170682.4(P2RX2):c.9C>T(p.Ala3=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00458 in 1,283,212 control chromosomes in the GnomAD database, including 238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 139 hom., cov: 29)

Exomes 𝑓: 0.0021 ( 99 hom. )

Consequence

P2RX2
NM_170682.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.60

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 12-132618825-C-T is Benign according to our data. Variant chr12-132618825-C-T is described in ClinVar as [Benign]. Clinvar id is 226991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.6 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX2	NM_170682.4 linkuse as main transcript	c.9C>T	p.Ala3=	synonymous_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.9C>T	p.Ala3=	synonymous_variant	1/11		NM_170682.4	ENSP00000494644	A2	Q9UBL9-1

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3453

AN:

150650

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0786

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00923

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000356

Gnomad OTH

AF:

0.0213

GnomAD3 exomes

AF:

0.00687

AC:

261

AN:

38008

Hom.:

AF XY:

0.00612

AC XY:

128

AN XY:

20898

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.00862

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:

0.000302

Gnomad OTH exome

AF:

0.00187

GnomAD4 exome

AF:

0.00214

AC:

2419

AN:

1132454

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

1074

AN XY:

545630

show subpopulations

Gnomad4 AFR exome

AF:

0.0813

Gnomad4 AMR exome

AF:

0.00608

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000965

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000200

Gnomad4 OTH exome

AF:

0.00498

GnomAD4 genome

AF:

0.0229

AC:

3456

AN:

150758

Hom.:

139

Cov.:

AF XY:

0.0220

AC XY:

1623

AN XY:

73648

show subpopulations

Gnomad4 AFR

AF:

0.0784

Gnomad4 AMR

AF:

0.00922

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000356

Gnomad4 OTH

AF:

0.0210

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.0252

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Ala3Ala in exon 1 of P2RX2: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 6.6% (223/3356) of Afr ican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs186684886). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2017	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.4

DANN

Benign

0.96

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