12-132620010-T-C

Position:

• chr12-132620010-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_170682.4(P2RX2):​c.468T>C​(p.Thr156=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,581,932 control chromosomes in the GnomAD database, including 299,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (35087 hom., cov: 33)
  • Exomes 𝑓: 0.61 (264714 hom.)
• Consequence: P2RX2 NM_170682.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -9.34

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 12-132620010-T-C is Benign according to our data. Variant chr12-132620010-T-C is described in ClinVar as [Benign]. Clinvar id is 226984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-9.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX2	NM_170682.4	c.468T>C	p.Thr156=	synonymous_variant	5/11	ENST00000643471.2	NP_733782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX2	ENST00000643471.2	c.468T>C	p.Thr156=	synonymous_variant	5/11		NM_170682.4	ENSP00000494644	A2

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101874 AN: 152028 Hom.: 35048 Cov.: 33

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.641

GnomAD3 exomes AF: 0.637 AC: 126913 AN: 199238 Hom.: 41423 AF XY: 0.624 AC XY: 67445 AN XY: 108014

Gnomad AFR exome AF: 0.805

Gnomad AMR exome AF: 0.790

Gnomad ASJ exome AF: 0.510

Gnomad EAS exome AF: 0.806

Gnomad SAS exome AF: 0.600

Gnomad FIN exome AF: 0.550

Gnomad NFE exome AF: 0.576

Gnomad OTH exome AF: 0.621

GnomAD4 exome AF: 0.605 AC: 865670 AN: 1429786 Hom.: 264714 Cov.: 43 AF XY: 0.604 AC XY: 427853 AN XY: 708406

Gnomad4 AFR exome AF: 0.810

Gnomad4 AMR exome AF: 0.780

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.807

Gnomad4 SAS exome AF: 0.596

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.591

Gnomad4 OTH exome AF: 0.612

GnomAD4 genome AF: 0.670 AC: 101968 AN: 152146 Hom.: 35087 Cov.: 33 AF XY: 0.670 AC XY: 49808 AN XY: 74388

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.805

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.644

Alfa AF: 0.614 Hom.: 15711

Bravo AF: 0.689

Asia WGS AF: 0.696 AC: 2419 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 23, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Thr156Thr in exon 5 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 41.8% (3583/8564) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs7964634). -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal dominant nonsyndromic hearing loss 41 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.13
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs7964634; hg19: chr12-133196596; COSMIC: COSV57675449; COSMIC: COSV57675449;