Variant 12-132618934-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2

The NM_170682.4(P2RX2):c.118C>A(p.Arg40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000085 in 1,176,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: not found (cov: 28)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

P2RX2
NM_170682.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.127

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3081751).

BP6

Variant 12-132618934-C-A is Benign according to our data. Variant chr12-132618934-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2551691.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX2	NM_170682.4 linkuse as main transcript	c.118C>A	p.Arg40Ser	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.118C>A	p.Arg40Ser	missense_variant	1/11		NM_170682.4	ENSP00000494644	A2	Q9UBL9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000260

AC:

AN:

115480

Hom.:

AF XY:

0.0000470

AC XY:

AN XY:

63864

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000501

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000850

AC:

AN:

1176460

Hom.:

Cov.:

AF XY:

0.0000105

AC XY:

AN XY:

570964

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:

0.00000831

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000252

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2023

The c.118C>A (p.R40S) alteration is located in exon 1 (coding exon 1) of the P2RX2 gene. This alteration results from a C to A substitution at nucleotide position 118, causing the arginine (R) at amino acid position 40 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 08, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

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

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.82

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

M_CAP

Pathogenic

0.77

MetaRNN

Benign

0.31

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L;L;L;L;L;.

MutationTaster

Benign

1.0

D;D;N;N;N;N;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.2

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

REVEL

Benign

0.090

Sift

Uncertain

0.0040

.;D;D;T;D;D;.

Sift4G

Benign

0.12

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

Polyphen

0.78

P;P;P;P;B;P;B

Vest4

0.31, 0.39, 0.38, 0.34, 0.32, 0.37

MutPred

0.56

Loss of MoRF binding (P = 0.0372);Loss of MoRF binding (P = 0.0372);Loss of MoRF binding (P = 0.0372);Loss of MoRF binding (P = 0.0372);Loss of MoRF binding (P = 0.0372);Loss of MoRF binding (P = 0.0372);Loss of MoRF binding (P = 0.0372);

MVP

0.51

MPC

1.4

ClinPred

0.37

GERP RS

3.1

Varity_R

0.39

gMVP

0.33

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

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