rs900907976
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PP5_ModerateBP4BP7
The NM_000552.5(VWF):c.7464C>T(p.Gly2488=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
VWF
NM_000552.5 synonymous
NM_000552.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.676
Genes affected
VWF (HGNC:12726): (von Willebrand factor) This gene encodes a glycoprotein involved in hemostasis. The encoded preproprotein is proteolytically processed following assembly into large multimeric complexes. These complexes function in the adhesion of platelets to sites of vascular injury and the transport of various proteins in the blood. Mutations in this gene result in von Willebrand disease, an inherited bleeding disorder. An unprocessed pseudogene has been found on chromosome 22. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP5
?
Variant 12-5971683-G-A is Pathogenic according to our data. Variant chr12-5971683-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 619755.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-5971683-G-A is described in Lovd as [Pathogenic]. Variant chr12-5971683-G-A is described in Lovd as [Pathogenic].
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).. Strength limited to SUPPORTING due to the PP5.
BP7
?
Synonymous conserved (PhyloP=-0.676 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VWF | NM_000552.5 | c.7464C>T | p.Gly2488= | synonymous_variant | 44/52 | ENST00000261405.10 | |
VWF | XM_047429501.1 | c.7464C>T | p.Gly2488= | synonymous_variant | 44/52 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VWF | ENST00000261405.10 | c.7464C>T | p.Gly2488= | synonymous_variant | 44/52 | 1 | NM_000552.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251270Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135844
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461848Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727220
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Apr 18, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at