rs151253585

Positions:

• chr12-132620110-C-A
• chr12-132620110-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_170682.4(P2RX2):​c.554+14C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 1,557,626 control chromosomes in the GnomAD database, including 447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (34 hom., cov: 33)
  • Exomes 𝑓: 0.021 (413 hom.)
• Consequence: P2RX2 NM_170682.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.48

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-132620110-C-A is Benign according to our data. Variant chr12-132620110-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 226985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX2	NM_170682.4	c.554+14C>A		intron_variant		ENST00000643471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX2	ENST00000643471.2	c.554+14C>A		intron_variant			NM_170682.4	A2

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2454 AN: 152152 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.00369

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.00612

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0268

GnomAD3 exomes AF: 0.0187 AC: 3180 AN: 170374 Hom.: 54 AF XY: 0.0190 AC XY: 1743 AN XY: 91864

Gnomad AFR exome AF: 0.00347

Gnomad AMR exome AF: 0.0140

Gnomad ASJ exome AF: 0.0642

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0103

Gnomad FIN exome AF: 0.00929

Gnomad NFE exome AF: 0.0251

Gnomad OTH exome AF: 0.0245

GnomAD4 exome AF: 0.0212 AC: 29750 AN: 1405358 Hom.: 413 Cov.: 32 AF XY: 0.0212 AC XY: 14702 AN XY: 695084

Gnomad4 AFR exome AF: 0.00477

Gnomad4 AMR exome AF: 0.0140

Gnomad4 ASJ exome AF: 0.0631

Gnomad4 EAS exome AF: 0.0000269

Gnomad4 SAS exome AF: 0.0110

Gnomad4 FIN exome AF: 0.00971

Gnomad4 NFE exome AF: 0.0226

Gnomad4 OTH exome AF: 0.0242

GnomAD4 genome AF: 0.0161 AC: 2451 AN: 152268 Hom.: 34 Cov.: 33 AF XY: 0.0154 AC XY: 1146 AN XY: 74442

Gnomad4 AFR AF: 0.00368

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.0700

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00828

Gnomad4 FIN AF: 0.00612

Gnomad4 NFE AF: 0.0241

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0178 Hom.: 9

Bravo AF: 0.0167

Asia WGS AF: 0.00520 AC: 19 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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	554+14C>A in intron 5 of P2RX2: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 2.4% (204/8534) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS; dbSNP rs151253585). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 06, 2017	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	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	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.63

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: rs151253585; hg19: chr12-133196696;