rs142844880

Variant names:

• chr12-132620033-A-G
• rs142844880
• NM_170682.4:c.491A>G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001282164.2(P2RX2):​c.386-2A>G variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,590,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: P2RX2 NM_001282164.2 splice_acceptor, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.27

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.340354).
• BP6: Variant 12-132620033-A-G is Benign according to our data. Variant chr12-132620033-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 501253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-132620033-A-G is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd4 at 140 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX2	NM_170682.4	c.491A>G	p.Gln164Arg	missense_variant	Exon 5 of 11	ENST00000643471.2	NP_733782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX2	ENST00000643471.2	c.491A>G	p.Gln164Arg	missense_variant	Exon 5 of 11		NM_170682.4	ENSP00000494644.1

Frequencies

GnomAD3 genomes AF: 0.000920 AC: 140 AN: 152094 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.000725 AC: 153 AN: 210910 Hom.: 1 AF XY: 0.000743 AC XY: 85 AN XY: 114416

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.000541

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000866

Gnomad OTH exome AF: 0.00204

GnomAD4 exome AF: 0.00106 AC: 1522 AN: 1438392 Hom.: 0 Cov.: 35 AF XY: 0.00103 AC XY: 737 AN XY: 713270

Gnomad4 AFR exome AF: 0.000121

Gnomad4 AMR exome AF: 0.00192

Gnomad4 ASJ exome AF: 0.000506

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000593

Gnomad4 NFE exome AF: 0.00125

Gnomad4 OTH exome AF: 0.000823

GnomAD4 genome AF: 0.000920 AC: 140 AN: 152210 Hom.: 0 Cov.: 33 AF XY: 0.000981 AC XY: 73 AN XY: 74410

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000897

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000804 Hom.: 0

Bravo AF: 0.00120

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000584 AC: 5

ExAC AF: 0.000382 AC: 46

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Sep 18, 2018

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.Gln164Arg variant in P2RX2 is classified as benign because it has been ide ntified in 0.18% (56/30374) of Latino chromosomes by gnomAD (http://gnomad.broad institute.org), and computational prediction tools and conservation analysis sug gest that this variant may not impact the protein. ACMG/AMP Criteria applied: BA 1, BP4. -

Jul 14, 2017

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Sep 25, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 18, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

P2RX2-related disorder Benign:1

Sep 14, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	0.092
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Benign	0.077	D
ClinPred		0.027	T
GERP RS		5.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs142844880; hg19: chr12-133196619;