12-5949091-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBS2_Supporting
The NM_000552.5(VWF):āc.8366C>Gā(p.Thr2789Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,614,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_000552.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000985 AC: 15AN: 152262Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251074Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135734
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727230
GnomAD4 genome AF: 0.0000984 AC: 15AN: 152380Hom.: 0 Cov.: 33 AF XY: 0.0000939 AC XY: 7AN XY: 74508
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: VWF c.8366C>G (p.Thr2789Ser) results in a conservative amino acid change located in the Cystine knot, C-terminal (IPR006207) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 251074 control chromosomes. c.8366C>G has been reported in the literature in individuals affected with Von Willebrand Disease (Borras_2017). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 28971901). ClinVar contains an entry for this variant (Variation ID: 310031). Based on the evidence outlined above, the variant was classified as uncertain significance. -
not provided Uncertain:1
In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28971901) -
Hereditary von Willebrand disease Uncertain:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at