Variant rs1555299245 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_170682.4(P2RX2):c.910G>A(p.Ala304Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

P2RX2
NM_170682.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.938

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX2	NM_170682.4 linkuse as main transcript	c.910G>A	p.Ala304Thr	missense_variant	9/11	ENST00000643471.2	NP_733782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX2	ENST00000643471.2 linkuse as main transcript	c.910G>A	p.Ala304Thr	missense_variant	9/11		NM_170682.4	ENSP00000494644	A2	Q9UBL9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jan 13, 2017

The p.Ala304Thr variant in P2RX2 has not been previously reported in individuals with hearing loss or in large population studies. Computational prediction tool s and conservation analysis suggest that the p.Ala304Thr variant may impact the protein, though this information is not predictive enough to determine pathogeni city. In summary, the clinical significance of the p.Ala304Thr variant is uncert ain. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.42

T;T;.;.;.;.;.;.;T

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

.;D;D;D;D;D;D;D;D

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.94

D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.7

M;M;.;M;.;.;.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.6

.;D;D;D;D;D;D;D;.

REVEL

Uncertain

0.50

Sift

Uncertain

0.0090

.;D;D;D;D;D;D;D;.

Sift4G

Uncertain

0.042

.;D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;D;D;D;D

Vest4

0.89, 0.56, 0.84, 0.82, 0.88, 0.93, 0.90, 0.83

MutPred

0.83

Gain of phosphorylation at A304 (P = 0.0349);Gain of phosphorylation at A304 (P = 0.0349);.;Gain of phosphorylation at A304 (P = 0.0349);.;.;.;Gain of phosphorylation at A304 (P = 0.0349);Gain of phosphorylation at A304 (P = 0.0349);

MVP

0.45

MPC

0.48

ClinPred

1.0

GERP RS

5.0

Varity_R

0.66

gMVP

0.90

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

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