rs143664462
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP4_StrongBP6_Very_StrongBS2
The NM_170682.4(P2RX2):c.211G>A(p.Glu71Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00266 in 1,612,632 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0028 ( 12 hom. )
Consequence
P2RX2
NM_170682.4 missense
NM_170682.4 missense
Scores
5
4
4
Clinical Significance
Conservation
PhyloP100: 4.18
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PP3
?
Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, Cadd, Dann, FATHMM_MKL, M_CAP, PrimateAI [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]
BP4
?
Computational evidence support a benign effect (MetaRNN=0.028756559).
BP6
?
Variant 12-132619476-G-A is Benign according to our data. Variant chr12-132619476-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 229124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-132619476-G-A is described in Lovd as [Likely_benign].
BS2
?
High AC in GnomAd4 at 230 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
P2RX2 | NM_170682.4 | c.211G>A | p.Glu71Lys | missense_variant | 2/11 | ENST00000643471.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
P2RX2 | ENST00000643471.2 | c.211G>A | p.Glu71Lys | missense_variant | 2/11 | NM_170682.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00151 AC: 230AN: 152022Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00156 AC: 390AN: 249322Hom.: 0 AF XY: 0.00155 AC XY: 209AN XY: 135248
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GnomAD4 exome AF: 0.00278 AC: 4057AN: 1460498Hom.: 12 Cov.: 33 AF XY: 0.00263 AC XY: 1914AN XY: 726634
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GnomAD4 genome ? AF: 0.00151 AC: 230AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.00136 AC XY: 101AN XY: 74376
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ESP6500AA
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ExAC
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181
Asia WGS
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | P2RX2: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 11, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 24, 2017 | p.Glu71Lys in exon 2 of P2RX2: This variant is not expected to have clinical sig nificance because it has been identified in 0.3% (334/125162) of European chromo somes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.o rg; dbSNP rs143664462). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
T;T;.;.;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
Polyphen
D;D;D;D;D;D;D
Vest4
0.59, 0.25, 0.52, 0.56, 0.53
MVP
0.63
MPC
2.0
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at