rs201474543
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_170682.4(P2RX2):c.964G>A(p.Gly322Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000205 in 1,614,040 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00021 ( 2 hom. )
Consequence
P2RX2
NM_170682.4 missense
NM_170682.4 missense
Scores
5
7
2
Clinical Significance
Conservation
PhyloP100: 6.84
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 -12 ACMG points.
BP6
?
Variant 12-132621313-G-A is Benign according to our data. Variant chr12-132621313-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 229125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
P2RX2 | NM_170682.4 | c.964G>A | p.Gly322Arg | missense_variant | 9/11 | ENST00000643471.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
P2RX2 | ENST00000643471.2 | c.964G>A | p.Gly322Arg | missense_variant | 9/11 | NM_170682.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152144Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000227 AC: 57AN: 251356Hom.: 1 AF XY: 0.000250 AC XY: 34AN XY: 135842
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GnomAD4 exome AF: 0.000213 AC: 311AN: 1461778Hom.: 2 Cov.: 34 AF XY: 0.000231 AC XY: 168AN XY: 727198
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GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152262Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 12AN XY: 74444
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 15, 2018 | p.Gly322Arg in exon 9 of P2RX2: This variant is classified as benign because it is presen tin 0.1% (32/30780) of South Asian chromosomes by the Genome Aggregati on Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs201474543), and o ur laboratory has observed a nonsegregation of the variant in an affected siblin g with hearing loss. ACMG/AMP criteria applied: BA1, BS4. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D;.;.;.;.;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;.;M;.;.;.;M;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
T
Polyphen
D;D;D;D;D;D;D;D;D
Vest4
0.96, 0.72, 0.94, 0.93, 0.94, 0.97
MutPred
Gain of MoRF binding (P = 0.0105);Gain of MoRF binding (P = 0.0105);.;Gain of MoRF binding (P = 0.0105);.;.;.;Gain of MoRF binding (P = 0.0105);Gain of MoRF binding (P = 0.0105);
MVP
0.66
MPC
0.55
ClinPred
D
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