chr12-132621888-T-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_170682.4(P2RX2):​c.1332T>A​(p.Pro444Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000518 in 1,608,504 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00029 ( 3 hom. )

Consequence

P2RX2
NM_170682.4 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -1.24
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP6
Variant 12-132621888-T-A is Benign according to our data. Variant chr12-132621888-T-A is described in ClinVar as [Benign]. Clinvar id is 226981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-132621888-T-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.24 with no splicing effect.
BS2
High AC in GnomAd4 at 407 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
P2RX2NM_170682.4 linkc.1332T>A p.Pro444Pro synonymous_variant Exon 11 of 11 ENST00000643471.2 NP_733782.1 Q9UBL9-1Q32MC3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
P2RX2ENST00000643471.2 linkc.1332T>A p.Pro444Pro synonymous_variant Exon 11 of 11 NM_170682.4 ENSP00000494644.1 Q9UBL9-1

Frequencies

GnomAD3 genomes
AF:
0.00272
AC:
407
AN:
149502
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0101
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000592
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:
0.0000147
Gnomad OTH
AF:
0.00242
GnomAD3 exomes
AF:
0.000735
AC:
184
AN:
250390
Hom.:
3
AF XY:
0.000546
AC XY:
74
AN XY:
135560
show subpopulations
Gnomad AFR exome
AF:
0.0104
Gnomad AMR exome
AF:
0.000463
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:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000292
AC:
426
AN:
1458884
Hom.:
3
Cov.:
34
AF XY:
0.000233
AC XY:
169
AN XY:
725944
show subpopulations
Gnomad4 AFR exome
AF:
0.0114
Gnomad4 AMR exome
AF:
0.000561
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:
0.00000360
Gnomad4 OTH exome
AF:
0.000648
GnomAD4 genome
AF:
0.00272
AC:
407
AN:
149620
Hom.:
2
Cov.:
33
AF XY:
0.00269
AC XY:
197
AN XY:
73180
show subpopulations
Gnomad4 AFR
AF:
0.0100
Gnomad4 AMR
AF:
0.000591
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00239
Alfa
AF:
0.000960
Hom.:
0

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Nov 22, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jan 09, 2019
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

not specified Benign:1
Nov 24, 2014
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Pro470Pro in exon 10B of P2RX2: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 1.8% (80/4404) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs116834114). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
0.10
DANN
Benign
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.18
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.

Other links and lift over

dbSNP: rs116834114; hg19: chr12-133198474; API