rs113782309

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000449132.6(P2RX2):c.592C>T(p.Pro198Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,614,036 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P198L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0055 ( 8 hom., cov: 34)

Exomes 𝑓: 0.00079 ( 5 hom. )

Consequence

P2RX2
ENST00000449132.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.396

Publications

3 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 (MetaRNN=0.0036708117).

BP6

Variant 12-132620508-C-T is Benign according to our data. Variant chr12-132620508-C-T is described in ClinVar as Benign. ClinVar VariationId is 226987.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 = 0.00551 (839/152332) while in subpopulation AFR AF = 0.0162 (675/41578). AF 95% confidence interval is 0.0152. There are 8 homozygotes in GnomAd4. There are 426 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High AC in GnomAd4 at 839 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX2	NM_170682.4 link	c.699C>T	p.Asp233Asp	synonymous_variant	Exon 7 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.699C>T	p.Asp233Asp	synonymous_variant	Exon 7 of 11		NM_170682.4	ENSP00000494644.1		Q9UBL9-1

Frequencies

GnomAD3 genomes

AF:

0.00547

AC:

832

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00180

AC:

452

AN:

251254

AF XY:

0.00142

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000413

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000789

AC:

1153

AN:

1461704

Hom.:

Cov.:

AF XY:

0.000704

AC XY:

512

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.0164

AC:

548

AN:

33478

American (AMR)

AF:

0.00302

AC:

135

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000421

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53276

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000309

AC:

344

AN:

1111970

Other (OTH)

AF:

0.00166

AC:

100

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

149

224

298

373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00551

AC:

839

AN:

152332

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

426

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0162

AC:

675

AN:

41578

American (AMR)

AF:

0.00745

AC:

114

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

68030

Other (OTH)

AF:

0.00568

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

122

162

203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00339

Hom.:

Bravo

AF:

0.00642

ESP6500AA

AF:

0.0170

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00184

AC:

223

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Asp233Asp in exon 7 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 1.7% (75/4406) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs113782309). -

Apr 14, 2020

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Sep 28, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.2

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.1

PhyloP100

-0.40

PROVEAN

Benign

-1.4

REVEL

Benign

0.12

Sift

Benign

0.27

Sift4G

Benign

0.44

Polyphen

0.99

Vest4

0.19

MVP

0.20

ClinPred

0.0027

GERP RS

1.7

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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