chr12-5949034-G-GGGGA
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PVS1_ModeratePP5_ModerateBS2_Supporting
The NM_000552.5(VWF):c.8419_8422dupTCCC(p.Pro2808LeufsTer24) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,466 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_000552.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VWF | NM_000552.5 | c.8419_8422dupTCCC | p.Pro2808LeufsTer24 | frameshift_variant | Exon 52 of 52 | ENST00000261405.10 | NP_000543.3 | |
VWF | XM_047429501.1 | c.8419_8422dupTCCC | p.Pro2808LeufsTer24 | frameshift_variant | Exon 52 of 52 | XP_047285457.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461252Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726872
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74362
ClinVar
Submissions by phenotype
VWF-related disorder Pathogenic:1
The VWF c.8419_8422dupTCCC variant is predicted to result in a frameshift and premature protein termination (p.Pro2808Leufs*24). XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX which is predicted to result in a frameshift and extension of the normal open reading frame (p.Pro2808Leufs*24) (the canonical stop codon is at position p.2814). This variant has been reported in individuals with von Willebrand disease 1 (James et al. 2007. PubMed ID: 17190853). This variant has also been reported in the homozygous or compound heterozygous states in multiple individuals with von Willebrand disease 3 (Bowman et al. 2013. PubMed ID: 23311757; Bowman et al. 2017. PubMed ID: 28453889). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at