Variant rs876657423 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_170682.4(P2RX2):c.1325_1335delCTGCCCCTTCT(p.Ser442fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,613,480 control chromosomes in the GnomAD database, including 29 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 14 hom., cov: 33)

Exomes 𝑓: 0.00085 ( 15 hom. )

Consequence

P2RX2
NM_170682.4 frameshift

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.17

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 -16 ACMG points.

BP6

Variant 12-132621877-ATCTCTGCCCCT-A is Benign according to our data. Variant chr12-132621877-ATCTCTGCCCCT-A is described in ClinVar as [Likely_benign]. Clinvar id is 226980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00892 (1358/152250) while in subpopulation AFR AF= 0.0312 (1297/41542). AF 95% confidence interval is 0.0298. There are 14 homozygotes in gnomad4. There are 643 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1358 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX2	NM_170682.4 link	c.1325_1335delCTGCCCCTTCT	p.Ser442fs	frameshift_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
P2RX2	ENST00000643471.2 link	c.1325_1335delCTGCCCCTTCT	p.Ser442fs	frameshift_variant	Exon 11 of 11		NM_170682.4	ENSP00000494644.1		Q9UBL9-1

Frequencies

GnomAD3 genomes

AF:

0.00893

AC:

1358

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0313

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

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:

0.0000882

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00236

AC:

591

AN:

250266

Hom.:

AF XY:

0.00169

AC XY:

229

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.0318

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.000982

GnomAD4 exome

AF:

0.000847

AC:

1237

AN:

1461230

Hom.:

AF XY:

0.000741

AC XY:

539

AN XY:

726950

show subpopulations

Gnomad4 AFR exome

AF:

0.0304

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.00172

GnomAD4 genome

AF:

0.00892

AC:

1358

AN:

152250

Hom.:

Cov.:

AF XY:

0.00863

AC XY:

643

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0312

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00480

Hom.:

Bravo

AF:

0.00965

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 11, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Feb 09, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Ala469SerfsX21 in exon 11 of P2RX2 : This variant is not expected to have clin ical significance because it has been identified in 3.4% (344/10052) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs150092274). This variant is located in the last exon of the gene that is alternatively spliced in some isoforms, and is likely to escape nonsens e mediated decay. -

Autosomal dominant nonsyndromic hearing loss 41

Benign:1

Aug 07, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

La Branchor

0.61

BranchPoint Hunter

3.0

Splicing

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