Variant chr12-132618821-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_170682.4(P2RX2):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000179 in 1,119,232 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

P2RX2
NM_170682.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX2	NM_170682.4 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/11	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.5C>T	p.Ala2Val	missense_variant	1/11		NM_170682.4	ENSP00000494644	A2	Q9UBL9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000179

AC:

AN:

1119232

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

537760

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000214

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

Ambry Genetics

May 20, 2024

The c.5C>T (p.A2V) alteration is located in exon 1 (coding exon 1) of the P2RX2 gene. This alteration results from a C to T substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

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

Eigen

Benign

0.071

Eigen_PC

Benign

0.088

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.69

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

M_CAP

Pathogenic

0.42

MetaRNN

Uncertain

0.53

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

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.3

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

MutationTaster

Benign

0.75

N;N;N;N;N;N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.69

.;N;N;N;N;N;N;N;N

REVEL

Benign

0.067

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.0060

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

Polyphen

1.0

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

Vest4

0.33, 0.33, 0.35, 0.28, 0.36, 0.33, 0.35, 0.31

MutPred

0.36

Gain of stability (P = 0.0174);Gain of stability (P = 0.0174);Gain of stability (P = 0.0174);Gain of stability (P = 0.0174);Gain of stability (P = 0.0174);Gain of stability (P = 0.0174);Gain of stability (P = 0.0174);Gain of stability (P = 0.0174);Gain of stability (P = 0.0174);

MVP

0.57

MPC

1.8

ClinPred

0.92

GERP RS

4.1

Varity_R

0.25

gMVP

0.41

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over