rs199712315

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_170682.4(P2RX2):c.1219G>A(p.Gly407Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,600,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

P2RX2
NM_170682.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -0.790

Publications

0 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:

ENSG00000280311 (HGNC:):

ENSG00000280311 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033161104).

BP6

Variant 12-132621775-G-A is Benign according to our data. Variant chr12-132621775-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 227828.

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX2	NM_170682.4 link	c.1219G>A	p.Gly407Ser	missense_variant	Exon 11 of 11	ENST00000643471.2	NP_733782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX2	ENST00000643471.2 link	c.1219G>A	p.Gly407Ser	missense_variant	Exon 11 of 11		NM_170682.4	ENSP00000494644.1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000457

AC:

AN:

240718

AF XY:

0.0000385

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000917

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000131

AC:

190

AN:

1448268

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

718812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33256

American (AMR)

AF:

0.00

AC:

AN:

43888

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25212

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39530

South Asian (SAS)

AF:

0.000107

AC:

AN:

84416

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.000147

AC:

162

AN:

1103988

Other (OTH)

AF:

0.000268

AC:

AN:

59764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000109

Hom.:

Bravo

AF:

0.0000793

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:1

Jun 19, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1297G>A (p.G433S) alteration is located in exon 10 (coding exon 10) of the P2RX2 gene. This alteration results from a G to A substitution at nucleotide position 1297, causing the glycine (G) at amino acid position 433 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Jun 18, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Gly433Ser in exon 10B of P2RX2: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, over 10 mammals including primates have a serine (Ser) at this position. It has also been identified in 7/116419 chromosomes by the Exome Aggregation Co nsortium Sequencing Project (ExAC, http://exac.broadinstitute.org; dbSNP rs19971 2315).

not provided

Benign:1

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

P2RX2: BP4, BP5

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.10

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.10

T;T;.;.;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.0

.;T;T;T;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.033

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;N;.;.;.;.

PhyloP100

-0.79

PrimateAI

Benign

0.33

PROVEAN

Benign

0.0

.;N;N;N;N;N

REVEL

Benign

0.0

Sift

Pathogenic

0.0

.;T;T;T;T;T

Sift4G

Pathogenic

0.0

.;T;T;T;T;T

Vest4

0.0

ClinPred

0.049

GERP RS

-6.3

Varity_R

0.040

gMVP

0.20

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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