1-1437103-AC-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_022834.5(VWA1):c.252delC(p.Glu85SerfsTer58) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000561 in 1,605,536 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_022834.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VWA1 | ENST00000476993.2 | c.252delC | p.Glu85SerfsTer58 | frameshift_variant | Exon 2 of 3 | 1 | NM_022834.5 | ENSP00000417185.1 | ||
VWA1 | ENST00000495558.1 | c.147delC | p.Glu50SerfsTer58 | frameshift_variant | Exon 2 of 2 | 2 | ENSP00000463643.1 | |||
VWA1 | ENST00000471398.1 | c.372delC | p.Glu125SerfsTer23 | frameshift_variant | Exon 2 of 2 | 3 | ENSP00000464343.1 | |||
VWA1 | ENST00000338660.5 | c.74-217delC | intron_variant | Intron 1 of 2 | 2 | ENSP00000423404.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000164 AC: 4AN: 244448Hom.: 0 AF XY: 0.0000226 AC XY: 3AN XY: 132866
GnomAD4 exome AF: 0.00000482 AC: 7AN: 1453336Hom.: 0 Cov.: 31 AF XY: 0.00000416 AC XY: 3AN XY: 721684
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
Neuromuscular disease Pathogenic:1
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not provided Pathogenic:1
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33693694, 33459760) -
Neuronopathy, distal hereditary motor, autosomal recessive 7 Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at