18-10789114-T-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PP3_ModeratePP5_Very_Strong
The NM_001378183.1(PIEZO2):c.2134A>G(p.Met712Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_001378183.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIEZO2 | NM_001378183.1 | c.2134A>G | p.Met712Val | missense_variant | Exon 15 of 56 | ENST00000674853.1 | NP_001365112.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIEZO2 | ENST00000674853.1 | c.2134A>G | p.Met712Val | missense_variant | Exon 15 of 56 | NM_001378183.1 | ENSP00000501957.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome Pathogenic:3
The c.2134A>G, p.Met712Val, variant found is located in exon 15 of the PIEZO2 gene. The variant found was reported de novo in a patient with no family history (ClinVar ID: 137633) (PS2). The variant found is not present in population-based databases such as GnomAD, ExAc, or 1000 Genomes (PM2_Supporting). In the PIEZO2 gene, missense variants are a frequent cause of pathology (PP2). Bioinformatics predictors classify the variant as deleted (PP3). The patient's phenotype is consistent with distal arthrogryposis type 5, and the PIEZO2 gene is closely associated with the pathology (PP4). A 21-year-old patient was being studied for suspected distal arthrogryposis. The patient presents short stature, arthrogryposis, campodactyly, clinodactyly, limited wrist extension, enophthalmos, and bilateral eyelid ptosis. -
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Inborn genetic diseases Pathogenic:1
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not provided Pathogenic:1
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26259784, 27743844, 30988732, 24726473, 15103714) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at