NM_022834.5:c.62_71delGCGCGGAGCG
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_022834.5(VWA1):c.62_71delGCGCGGAGCG(p.Gly21AlafsTer12) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000424 in 1,202,298 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Consequence
NM_022834.5 frameshift, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VWA1 | NM_022834.5 | c.62_71delGCGCGGAGCG | p.Gly21AlafsTer12 | frameshift_variant, splice_region_variant | Exon 1 of 3 | ENST00000476993.2 | NP_073745.2 | |
VWA1 | NM_199121.3 | c.62_71delGCGCGGAGCG | p.Gly21AlafsTer291 | frameshift_variant, splice_region_variant | Exon 1 of 3 | NP_954572.2 | ||
LOC107985729 | XM_017003066.2 | c.*649_*658delGGCGCGGAGC | downstream_gene_variant | XP_016858555.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VWA1 | ENST00000476993.2 | c.62_71delGCGCGGAGCG | p.Gly21AlafsTer12 | frameshift_variant, splice_region_variant | Exon 1 of 3 | 1 | NM_022834.5 | ENSP00000417185.1 | ||
VWA1 | ENST00000471398.1 | c.62_71delGCGCGGAGCG | p.Gly21AlafsTer52 | frameshift_variant, splice_region_variant | Exon 1 of 2 | 3 | ENSP00000464343.1 | |||
VWA1 | ENST00000338660.5 | c.62_71delGCGCGGAGCG | p.Gly21AlafsTer291 | frameshift_variant, splice_region_variant | Exon 1 of 3 | 2 | ENSP00000423404.1 | |||
VWA1 | ENST00000495558.1 | c.-33+664_-33+673delGCGCGGAGCG | intron_variant | Intron 1 of 1 | 2 | ENSP00000463643.1 |
Frequencies
GnomAD3 genomes AF: 0.0000468 AC: 7AN: 149504Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000418 AC: 44AN: 1052794Hom.: 0 AF XY: 0.0000489 AC XY: 25AN XY: 511400
GnomAD4 genome AF: 0.0000468 AC: 7AN: 149504Hom.: 0 Cov.: 32 AF XY: 0.0000137 AC XY: 1AN XY: 72886
ClinVar
Submissions by phenotype
Neuronopathy, distal hereditary motor, autosomal recessive 7 Pathogenic:2
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The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with VWA1-related disorder (ClinVar ID: VCV000830324 /PMID: 33459760). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. -
Neuromuscular disease Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at