rs878853135
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP5
The NM_001378183.1(PIEZO2):c.8547del(p.Tyr2850IlefsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
PIEZO2
NM_001378183.1 frameshift
NM_001378183.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.832
Genes affected
PIEZO2 (HGNC:26270): (piezo type mechanosensitive ion channel component 2) The protein encoded by this gene contains more than thirty transmembrane domains and likely functions as part of mechanically-activated (MA) cation channels. These channels serve to connect mechanical forces to biological signals. The encoded protein quickly adapts MA currents in somatosensory neurons. Defects in this gene are a cause of type 5 distal arthrogryposis. Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 3069 codons.
PP5
?
Variant 18-10671577-AT-A is Pathogenic according to our data. Variant chr18-10671577-AT-A is described in ClinVar as [Pathogenic]. Clinvar id is 235838.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr18-10671577-AT-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIEZO2 | NM_001378183.1 | c.8547del | p.Tyr2850IlefsTer7 | frameshift_variant | 56/56 | ENST00000674853.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIEZO2 | ENST00000674853.1 | c.8547del | p.Tyr2850IlefsTer7 | frameshift_variant | 56/56 | NM_001378183.1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | Jun 04, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at