rs144072210
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBS2_Supporting
The NM_000552.5(VWF):āc.5851A>Gā(p.Thr1951Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000437 in 1,611,706 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000552.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VWF | NM_000552.5 | c.5851A>G | p.Thr1951Ala | missense_variant | 35/52 | ENST00000261405.10 | |
VWF | XM_047429501.1 | c.5851A>G | p.Thr1951Ala | missense_variant | 35/52 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VWF | ENST00000261405.10 | c.5851A>G | p.Thr1951Ala | missense_variant | 35/52 | 1 | NM_000552.5 | P1 | |
VWF | ENST00000538635.5 | n.421-2280A>G | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000532 AC: 81AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000558 AC: 138AN: 247230Hom.: 0 AF XY: 0.000547 AC XY: 73AN XY: 133576
GnomAD4 exome AF: 0.000428 AC: 624AN: 1459526Hom.: 1 Cov.: 32 AF XY: 0.000433 AC XY: 314AN XY: 725884
GnomAD4 genome ? AF: 0.000532 AC: 81AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34AN XY: 74354
ClinVar
Submissions by phenotype
Abnormality of coagulation Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | NIHR Bioresource Rare Diseases, University of Cambridge | Feb 01, 2019 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 09, 2022 | Variant summary: VWF c.5851A>G (p.Thr1951Ala) results in a non-conservative amino acid change located in the von Willebrand factor, type D domain (IPR001846) 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 0.00065 in 278632 control chromosomes (gnomAD), predominantly at a frequency of 0.0011 within the Non-Finnish European subpopulation in the gnomAD database. c.5851A>G has been reported in the literature in individuals affected with Von Willebrand Disease (Kakela_2006, Johansson_2011, Bastarache_2018, Downes_2019, Sadler_2021). The variant was also found occuring in unaffected family members (Kakela_2006) and in unrelated individuals without disease (Sadler_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic and three as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. - |
von Willebrand disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 26, 2022 | - - |
von Willebrand disease type 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Center for Precision Medicine, Vanderbilt University Medical Center | Mar 16, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2019 | - - |
von Willebrand disease type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Laboratory of Hematology, Radboud University Medical Center | Apr 12, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at