rs151253585

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.48

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 41
Inheritance: AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

P2RX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
P2RX2	NM_170682.4 link	c.554+14C>A		intron_variant	Intron 5 of 10	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.554+14C>A		intron_variant	Intron 5 of 10		NM_170682.4	ENSP00000494644.1		Q9UBL9-1

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2454

AN:

152152

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0187

AC:

3180

AN:

170374

AF XY:

0.0190

show subpopulations

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 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.:

AF XY:

0.0212

AC XY:

14702

AN XY:

695084

show subpopulations

African (AFR)

AF:

0.00477

AC:

154

AN:

32290

American (AMR)

AF:

0.0140

AC:

517

AN:

37050

Ashkenazi Jewish (ASJ)

AF:

0.0631

AC:

1580

AN:

25052

East Asian (EAS)

AF:

0.0000269

AC:

AN:

37146

South Asian (SAS)

AF:

0.0110

AC:

880

AN:

80264

European-Finnish (FIN)

AF:

0.00971

AC:

475

AN:

48902

Middle Eastern (MID)

AF:

0.0637

AC:

317

AN:

4976

European-Non Finnish (NFE)

AF:

0.0226

AC:

24417

AN:

1081440

Other (OTH)

AF:

0.0242

AC:

1409

AN:

58238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1723

3446

5170

6893

8616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

918

1836

2754

3672

4590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0161

AC:

2451

AN:

152268

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

1146

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00368

AC:

153

AN:

41548

American (AMR)

AF:

0.0148

AC:

227

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0700

AC:

243

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00828

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00612

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0241

AC:

1641

AN:

68006

Other (OTH)

AF:

0.0265

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

127

254

380

507

634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0178

Hom.:

Bravo

AF:

0.0167

Asia WGS

AF:

0.00520

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 16, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Jul 06, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.7

(source)

DANN

Benign

0.63

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over