rs75585377
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_012226.5(P2RX2):c.118C>T(p.Arg40Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,612,196 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 9 hom., cov: 32)
Exomes 𝑓: 0.015 ( 147 hom. )
Consequence
P2RX2
NM_012226.5 missense
NM_012226.5 missense
Scores
1
4
9
Clinical Significance
Conservation
PhyloP100: 0.180
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 -16 ACMG points.
BP6
Variant 12-132619451-C-T is Benign according to our data. Variant chr12-132619451-C-T is described in ClinVar as [Benign]. Clinvar id is 226983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-132619451-C-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0149 (21786/1460106) while in subpopulation SAS AF= 0.0163 (1403/86248). AF 95% confidence interval is 0.0161. There are 147 homozygotes in gnomad4_exome. There are 10965 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1574 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0104 AC: 1574AN: 151982Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.0112 AC: 2778AN: 248670Hom.: 19 AF XY: 0.0120 AC XY: 1621AN XY: 135026
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GnomAD4 exome AF: 0.0149 AC: 21786AN: 1460106Hom.: 147 Cov.: 33 AF XY: 0.0151 AC XY: 10965AN XY: 726432
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GnomAD4 genome AF: 0.0103 AC: 1574AN: 152090Hom.: 9 Cov.: 32 AF XY: 0.00990 AC XY: 736AN XY: 74336
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | P2RX2: BP4, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Ile62Ile in exon 2 of P2RX2: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 1.5% (133/8600) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs75585377). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 02, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
P2RX2-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 15, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
ClinPred
T
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 7
Find out detailed SpliceAI scores and Pangolin per-transcript scores at