rs886039822
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_001378183.1(PIEZO2):c.4798C>T(p.Arg1600Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000505 in 1,384,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001378183.1 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIEZO2 | NM_001378183.1 | c.4798C>T | p.Arg1600Ter | stop_gained | 34/56 | ENST00000674853.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIEZO2 | ENST00000674853.1 | c.4798C>T | p.Arg1600Ter | stop_gained | 34/56 | NM_001378183.1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000505 AC: 7AN: 1384882Hom.: 0 Cov.: 31 AF XY: 0.00000585 AC XY: 4AN XY: 683370
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 25, 2019 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PIEZO2 are known to be pathogenic (PMID: 27653382, 27843126). This variant has been observed in individual(s) with arthrogryposis with impaired proprioception and touch (PMID: 27653382). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 265868). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg1575*) in the PIEZO2 gene. It is expected to result in an absent or disrupted protein product. - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 07, 2019 | - - |
Arthrogryposis, distal, with impaired proprioception and touch Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 11, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at