rs61754002
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000552.5(VWF):c.1071C>A(p.Tyr357*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
VWF
NM_000552.5 stop_gained
NM_000552.5 stop_gained
Scores
2
3
2
Clinical Significance
Conservation
PhyloP100: 1.25
Publications
2 publications found
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]
VWF Gene-Disease associations (from GenCC):
- hereditary von Willebrand diseaseInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- von Willebrand disease type 2BInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- von Willebrand disease 2Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
- von Willebrand disease 1Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
- von Willebrand disease type 2AInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- von Willebrand disease type 2MInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- von Willebrand disease 3Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- von Willebrand disease type 2NInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-6072369-G-T is Pathogenic according to our data. Variant chr12-6072369-G-T is described in CliVar as Pathogenic. Clinvar id is 316.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-6072369-G-T is described in CliVar as Pathogenic. Clinvar id is 316.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-6072369-G-T is described in CliVar as Pathogenic. Clinvar id is 316.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-6072369-G-T is described in CliVar as Pathogenic. Clinvar id is 316.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
von Willebrand disease type 2N Pathogenic:1
Nov 01, 2002
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
not provided Other:1
-
Academic Unit of Haematology, University of Sheffield
Significance:not provided
Review Status:no classification provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
PhyloP100
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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