ClinVar Genomic variation as it relates to human health
NM_000552.5(VWF):c.2561G>A (p.Arg854Gln)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000552.5(VWF):c.2561G>A (p.Arg854Gln)
Variation ID: 296 Accession: VCV000000296.82
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 12p13.31 12: 6034812 (GRCh38) [ NCBI UCSC ] 12: 6143978 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 May 12, 2024 Mar 19, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000552.5:c.2561G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000543.3:p.Arg854Gln missense NC_000012.12:g.6034812C>T NC_000012.11:g.6143978C>T NG_009072.2:g.94859G>A LRG_587:g.94859G>A LRG_587t1:c.2561G>A LRG_587p1:p.Arg854Gln P04275:p.Arg854Gln - Protein change
- R854Q
- Other names
- p.R854Q
- Canonical SPDI
- NC_000012.12:6034811:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00180 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00180
1000 Genomes Project 30x 0.00187
Exome Aggregation Consortium (ExAC) 0.00308
The Genome Aggregation Database (gnomAD), exomes 0.00340
Trans-Omics for Precision Medicine (TOPMed) 0.00351
The Genome Aggregation Database (gnomAD) 0.00377
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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VWF | - | - |
GRCh38 GRCh37 |
1476 | 1530 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Nov 4, 2022 | RCV000000320.12 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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May 4, 2022 | RCV000000321.18 | |
Pathogenic (16) |
criteria provided, multiple submitters, no conflicts
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Feb 6, 2024 | RCV000086620.57 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Mar 19, 2024 | RCV000169683.23 | |
Pathogenic/Likely pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Nov 30, 2023 | RCV000336497.22 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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May 3, 2023 | RCV000762901.12 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Feb 1, 2019 | RCV000851593.9 | |
Likely pathogenic (1) |
no assertion criteria provided
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May 1, 2020 | RCV001270529.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 2, 2024 | RCV003415598.5 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 16, 2024 | RCV003987302.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
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von Willebrand Disease
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000380622.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Comment:
The c.2561G>A (p.Arg854Gln) variant is found specifically in patients with type 2N von Willebrand disease (VWD) which manifests as a mild form of VWD with … (more)
The c.2561G>A (p.Arg854Gln) variant is found specifically in patients with type 2N von Willebrand disease (VWD) which manifests as a mild form of VWD with only moderate bleeding in homozygotes. This variant is well-documented as disease-causing for this specific type of VWD, found in up to 73% of type 2N patients to date (Casonato et al. 2013). The variant is also common among Caucasians, being found in over 1% of the general population (Goodeve et al. 2010). Across a selection of the available literature, the p.Arg854Gln variant has been reported in seven studies and found in a total of 72 patients including in 26 in a homozygous state, 12 in a compound heterozygous state and 34 in a heterozygous state in whom a second variant as not been found (Gaucher et al. 1991; Cacheris et al. 1991; Peerlinck et al. 1992; Hilbert et al. 2004; Hilbert et al. 2006; Veyradier et al. 2011; Casonato et al. 2013). The variant was absent from 906 control alleles and is reported at a frequency of 0.014 in the Puerto Rican population of the 1000 Genomes Project. Functional studies have demonstrated that the p.Arg854Gln variant results in reduced binding of FVIII and proteolysis by ADAMTS13 with a normal multimer pattern (Gaucher et al. 1991; Cacheris et al. 1991; Peerlinck et al. 1992; Hilbert et al. 2004; Hilbert et al. 2006; Skipwith et al. 2013; Wang et al. 2013). Based on the collective evidence, the p.Arg854Gln variant is classified as pathogenic for von Willebrand disease. (less)
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Pathogenic
(Apr 18, 2017)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000610065.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Pathogenic
(Nov 11, 2019)
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criteria provided, single submitter
Method: clinical testing
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von Willebrand disease type 2N
Affected status: yes
Allele origin:
germline
|
Versiti Diagnostic Laboratories, Versiti, Inc
Accession: SCV001250572.1
First in ClinVar: May 12, 2020 Last updated: May 12, 2020 |
Comment:
The missense variant VWF c.2561G>A, p.Arg854Gln (p.R854Q) in exon 20 changes amino acid arginine at codon 854 to glutamine. The arginine at this residue is … (more)
The missense variant VWF c.2561G>A, p.Arg854Gln (p.R854Q) in exon 20 changes amino acid arginine at codon 854 to glutamine. The arginine at this residue is highly conserved among species. This amino acid change occurs in the D'D3 domain of the VWF protein, a functional domain that binds factor VIII (Springer, 2014). Pathogenic variants in VWF are associated with autosomal dominant or autosomal recessive von Willebrand disease (VWD), characterized by quantitative or qualitative deficiencies in von Willebrand factor and resulting in prolonged bleeding. Pathogenic missense variants in the D'D3 domain have been shown to cause autosomal recessive type 2N VWD, characterized by low plasma factor VIII levels and a laboratory phenotype that can initially resemble hemophilia A. This sequence variant has is one of the most common reported variants in patients with type 2N VWD (Hilbert, 2004; Goodeve, 2007; Veyradier, 2011; van Meegeren, 2015; Borras, 2017). Functional studies of p.R854Q mutant in mamalian cells showed decreased FVIII binding (Hilbert, 2004; Swystun, 2017). The minor allele frequency of this variant in the general population is 0.003465 (gnomAD). In summary, the collective evidence supports VWF c.2561G>A, p.Arg854Gln as a pathogenic variant for type 2N von Willebrand disease. (less)
Number of individuals with the variant: 34
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Pathogenic
(-)
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criteria provided, single submitter
Method: research
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von Willebrand disease type 2
Affected status: no
Allele origin:
germline
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UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill
Study: NSIGHT-NC NEXUS
Accession: SCV001251482.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020
Comment:
carrier finding
|
Comment:
The (p.R854Q) variant in the VWF gene is the most frequent cause of VWD type 2N, which manifests as a mild form of VWD with … (more)
The (p.R854Q) variant in the VWF gene is the most frequent cause of VWD type 2N, which manifests as a mild form of VWD with only moderate bleeding in homozygotes (PMID: 20301765). (less)
Number of individuals with the variant: 2
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Pathogenic
(Feb 10, 2020)
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criteria provided, single submitter
Method: clinical testing
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von Willebrand disease type 2
Affected status: unknown
Allele origin:
germline
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Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV001425379.1
First in ClinVar: Aug 01, 2020 Last updated: Aug 01, 2020 |
Comment:
c.2561G>A (p.Arg854Gln) has been reported in the literature associated with von Willebrand disease, type 2N and functional analysis supports the deleterious nature of this variant. … (more)
c.2561G>A (p.Arg854Gln) has been reported in the literature associated with von Willebrand disease, type 2N and functional analysis supports the deleterious nature of this variant. Additionally, this variant (rs41276738) is more prevalent in affected individuals than the healthy population (gnomAD: 980/282824 total alleles; 0.3465%; 5 homozygotes). Sixteen submitters in ClinVar classify this variant as either pathogenic or likely pathogenic. We consider this variant to be pathogenic. (less)
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Pathogenic
(Mar 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001716116.2
First in ClinVar: Jun 15, 2021 Last updated: May 27, 2023 |
Number of individuals with the variant: 1
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Pathogenic
(Dec 09, 2021)
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criteria provided, single submitter
Method: research
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von Willebrand disease type 2
Affected status: yes
Allele origin:
germline
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Laboratory of Hematology, Radboud University Medical Center
Study: WIN study
Accession: SCV002546263.1 First in ClinVar: Jul 17, 2022 Last updated: Jul 17, 2022 |
Number of individuals with the variant: 7
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Pathogenic
(Sep 27, 2021)
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criteria provided, single submitter
Method: clinical testing
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von Willebrand disease type 1
von Willebrand disease type 3 von Willebrand disease type 2
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000893311.2
First in ClinVar: Mar 31, 2019 Last updated: Dec 31, 2022 |
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Pathogenic
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002011305.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Pathogenic
(Oct 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000322001.12
First in ClinVar: Feb 21, 2014 Last updated: Nov 25, 2023 |
Comment:
Published functional studies demonstrate a damaging effect with dramatically diminished capacity of VWF to bind factor VIII (PMID: 23636243, 1906877, 12588349); This variant is associated … (more)
Published functional studies demonstrate a damaging effect with dramatically diminished capacity of VWF to bind factor VIII (PMID: 23636243, 1906877, 12588349); This variant is associated with the following publications: (PMID: 26207643, 26105150, 26764160, 31064749, 20981092, 21489050, 21371195, 22197721, 23636243, 22875612, 22995991, 24029428, 25649154, 16953269, 9684781, 24033266, 20409624, 1906877, 23426949, 1832934, 1581215, 15461624, 25212677, 28436749, 29115006, 29220693, 29431110, 30609409, 30431218, 30722078, 31019283, 32935436, 31980526, 34426522, 31589614, 8115998, 9692396, 33942438, 33556167, 12588349, 20586924) (less)
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Pathogenic
(Jun 12, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000889897.3
First in ClinVar: Dec 15, 2018 Last updated: Jan 06, 2024 |
Comment:
In the published literature, this variant has been reported in multiple individuals with autosomal recessive Type 2N von Willebrand disease (Type 2N vWD) (PMID: 1832934 … (more)
In the published literature, this variant has been reported in multiple individuals with autosomal recessive Type 2N von Willebrand disease (Type 2N vWD) (PMID: 1832934 (1991), 9684781 (1998), 12353087 (2002), 15461624 (2004), 20409624 (2010)). Functional studies have shown that this variant greatly reduces the ability of the VWF protein to bind factor VIII (PMID: 1906877 (1991), 15461624 (2004)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Jan 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002020886.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
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Pathogenic
(Feb 06, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004243463.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
|
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Pathogenic
(Oct 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000605594.4
First in ClinVar: Sep 30, 2017 Last updated: Feb 20, 2024 |
Comment:
The VWF c.2561G>A; p.Arg854Gln variant (also known as Arg91Gln) is published in the literature in individuals with von Willebrand disease (VWD) type 2N and is … (more)
The VWF c.2561G>A; p.Arg854Gln variant (also known as Arg91Gln) is published in the literature in individuals with von Willebrand disease (VWD) type 2N and is the most common VWD type 2N pathogenic variant (Casonato 2018, Veyradier 2011, Wang 2013). Functional analyses of the variant protein show decreased factor VIII binding, consistent with VWD type 2N (Veyradier 2011, Wang 2013). This variant is reported in ClinVar (Variation ID: 296). This variant is found in the general population with an overall allele frequency of .347% (980/ 282824 alleles, including 5 homozygotes) in the Genome Aggregation Database. The arginine at codon 854 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.487). Considering available information, this variant is classified as pathogenic. References: Casonato A et al. Type 2N von Willebrand disease: Characterization and diagnostic difficulties. Haemophilia. 2018 Jan;24(1):134-140. Veyradier A et al. Validation of the first commercial ELISA for type 2N von Willebrand's disease diagnosis. Haemophilia. 2011. 17(6):944-51. Wang JW et al. Analysis of the storage and secretion of von Willebrand factor in blood outgrowth endothelial cells derived from patients with von Willebrand disease. Blood. 2013. 121(14):2762-72. (less)
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Pathogenic
(Feb 02, 2024)
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criteria provided, single submitter
Method: clinical testing
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VWF-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004117618.2
First in ClinVar: Nov 20, 2023 Last updated: Mar 16, 2024 |
Comment:
The VWF c.2561G>A variant is predicted to result in the amino acid substitution p.Arg854Gln. This variant (aka p.Arg91Gln) has been reported in the homozygous or … (more)
The VWF c.2561G>A variant is predicted to result in the amino acid substitution p.Arg854Gln. This variant (aka p.Arg91Gln) has been reported in the homozygous or compound heterozygous state in many patients with recessive von Willebrand disease (VWD) type 2N (van Meergeren et al. 2015. PubMed ID: 26207643; Castaman et al. 2010. PubMed ID: 20586924; Gaucher et al. 1991. PubMed ID: 1832934; Hilbert et al. 2004. PubMed ID: 15461624). One patient with VWD type 1 was also reported to have the p.Arg854Gln substitution (Peerlinck et al. 1992. PubMed ID: 1581215). Different cellular and biochemical studies indicate the p.Arg854Gln change alters normal VWF protein function (Cacheris et al. 1991. PubMed ID: 1906877; Castaman et al. 2010. PubMed ID: 20586924; Wang et al. 2013. PubMed ID: 23426949; Hilbert et al. 2004. PubMed ID: 15461624). This variant is reported in 0.57% of alleles in individuals of European (Finnish) descent in gnomAD, including several homozygotes. Multiple laboratories classify this variant as pathogenic or likely pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/296/). This variant is interpreted as pathogenic. (less)
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Pathogenic
(Jan 16, 2024)
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criteria provided, single submitter
Method: clinical testing
|
von Willebrand disorder
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004803450.1
First in ClinVar: Mar 30, 2024 Last updated: Mar 30, 2024 |
Comment:
Variant summary: VWF c.2561G>A (p.Arg854Gln) results in a conservative amino acid change located in the VWFC domain (IPR001846) of the encoded protein sequence. Three of … (more)
Variant summary: VWF c.2561G>A (p.Arg854Gln) results in a conservative amino acid change located in the VWFC domain (IPR001846) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0034 in 251418 control chromosomes in the gnomAD database, including 5 homozygotes. c.2561G>A has been reported in the literature as a homozygous and compound heterozygous genotype in multiple individuals affected with Von Willebrand Disease type 2N (e.g. Casonato_2013, Fidalgo_2016) and is a common variant associated with type 2N VWD. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, showing that the variant affects protein function (Wang_2013, Skipwith_2013). The following publications have been ascertained in the context of this evaluation (PMID: 22875612, 26988807, 23636243, 23426949). ClinVar contains an entry for this variant (Variation ID: 296). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Mar 19, 2024)
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criteria provided, single submitter
Method: clinical testing
|
Hereditary von Willebrand disease
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000221221.5
First in ClinVar: Apr 01, 2015 Last updated: Apr 20, 2024 |
Comment:
The p.Arg854Gln has been reported in the homozygous or compound heterozygous state in >20 individuals with von Willebrand disease (VWD) type 2N (Gaucher 1991 PMID: … (more)
The p.Arg854Gln has been reported in the homozygous or compound heterozygous state in >20 individuals with von Willebrand disease (VWD) type 2N (Gaucher 1991 PMID: 1832934, Peerlinck 1992 PMID: 1581215, Veyradier 2011 PMID: 21371195). This variant is a common disease-causing variant for type 2N VWD (Casonato 2013 PMID: 22875612). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID: 296) and has been identified in 0.6% (7050/1180026) of European chromosomes, including 26 total homozygotes by gnomAD (http://gnomad.broadinstitute.org, v.4.0.0). This is consistent with a recessive carrier frequency and the clinical manifestations of type 2N VWD. In vitro functional studies indicate the p.Arg854Gln variant may affect protein function as it has been shown to decrease binding to factor VIII (Wang 2012 PMID: 23426949, Skipwith 2013 PMID: 23636243). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive type 2N von Willebrand disease. ACMG/AMP criteria applied: PM3_VeryStrong, PS3_Supporting, PM2_Supporting. (less)
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Pathogenic
(Sep 14, 2015)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000334295.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 5
Sex: mixed
|
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Pathogenic
(Nov 21, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
von Willebrand disease type 2
Affected status: unknown
Allele origin:
unknown
|
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV000883107.1
First in ClinVar: Dec 15, 2018 Last updated: Dec 15, 2018 |
|
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Pathogenic
(Feb 01, 2019)
|
criteria provided, single submitter
Method: research
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von Willebrand disorder
Affected status: yes
Allele origin:
unknown
|
NIHR Bioresource Rare Diseases, University of Cambridge
Study: ThromboGenomics
Accession: SCV000899325.1 First in ClinVar: Sep 29, 2019 Last updated: Sep 29, 2019 |
Observation 1: Observation 2: Observation 3:
Sex: female
Ethnicity/Population group: European
Observation 4:
Sex: female
Ethnicity/Population group: European
Observation 5:
Sex: female
Ethnicity/Population group: European
Observation 6:
Sex: male
Ethnicity/Population group: European
Observation 7:
Sex: male
Ethnicity/Population group: European
Observation 8:
Sex: female
Ethnicity/Population group: European
Observation 9:
Sex: male
Ethnicity/Population group: European
Observation 10:
Sex: male
Ethnicity/Population group: European
|
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Likely pathogenic
(Feb 01, 2019)
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criteria provided, single submitter
Method: research
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Abnormality of coagulation
Affected status: yes
Allele origin:
unknown
|
NIHR Bioresource Rare Diseases, University of Cambridge
Study: ThromboGenomics
Accession: SCV000899326.1 First in ClinVar: Sep 29, 2019 Last updated: Sep 29, 2019 |
Observation 1:
Sex: female
Ethnicity/Population group: European
Observation 2:
Sex: male
Ethnicity/Population group: European
Observation 3:
Sex: female
Ethnicity/Population group: European
Observation 4:
Sex: female
Ethnicity/Population group: European
Observation 5:
Sex: male
Ethnicity/Population group: European
|
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Likely pathogenic
(Nov 26, 2021)
|
criteria provided, single submitter
Method: clinical testing
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von Willebrand disease type 2
Affected status: yes
Allele origin:
inherited
|
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn
Accession: SCV002103046.1
First in ClinVar: Mar 12, 2022 Last updated: Mar 12, 2022 |
Comment:
PS1_moderate, PS3, PM1
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Pathogenic
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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von Willebrand disease type 1
Affected status: unknown
Allele origin:
germline
|
Mendelics
Accession: SCV002519962.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
|
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Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
von Willebrand disease type 2
Affected status: yes
Allele origin:
germline
|
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology
Accession: SCV002569916.1
First in ClinVar: Sep 10, 2022 Last updated: Sep 10, 2022
Comment:
Submitted to GoldVariant by Kathleen Freson, Center for Molecular and Vascular Biology, Leuven, Belgium
|
Observation 1:
Clinical Features:
Low von Willebrand antigen and activity (present) , Low factor VIII (present)
Observation 2:
Clinical Features:
Thrombocytopenia (present) , Normal von Willebrand antigen and activity (present)
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Pathogenic
(Nov 04, 2022)
|
criteria provided, single submitter
Method: clinical testing
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von Willebrand disease type 2N
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Variantyx, Inc.
Accession: SCV002754530.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
This is a nonsynonymous variant in the VWF gene (OMIM 613160). Pathogenic variants in this gene have been associated with autosomal dominant and autosomal recessive … (more)
This is a nonsynonymous variant in the VWF gene (OMIM 613160). Pathogenic variants in this gene have been associated with autosomal dominant and autosomal recessive von Willebrand disease (VWD). This variant, also known as p.Arg91Gln, is the most common pathogenic variant associated with autosomal recessive VWD type 2N (VWD2N) (PMID: 15461624, 1832934, 21371195, 22875612, 26764160 31064749, 34355501) (PM3_Very Strong). Functional studies have shown that this variant alters VWF protein function (PMID: 12176890, 1918030, 31349985) (PS3). Multiple computational algorithms predict a deleterious effect for this substitution (PP3). This variant has a 0.6055% maximum allele frequency in non-founder control populations (https://gnomad.broadinstitute.org/). Based on the current evidence, this variant is classified as pathogenic for autosomal recessive VWD2N. (less)
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Pathogenic
(Jul 13, 2020)
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criteria provided, single submitter
Method: clinical testing
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von Willebrand disease type 1
Affected status: unknown
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556468.2
First in ClinVar: Aug 08, 2022 Last updated: Dec 17, 2022 |
Comment:
The VWF c.2561G>A variant is classified as Pathogenic (PS3, PS4, PP1, PP2, PP3, PP5)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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von Willebrand disease type 1
Affected status: yes
Allele origin:
germline
|
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology
Accession: SCV002500928.2
First in ClinVar: Apr 23, 2022 Last updated: Jul 22, 2023
Comment:
Submitted to the GoldVariant database by Kathleen Freson, Center for Molecular and Vascular Biology
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Clinical Features:
bleeding (present)
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Pathogenic
(May 03, 2023)
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criteria provided, single submitter
Method: clinical testing
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von Willebrand disease type 1
von Willebrand disease type 3 von Willebrand disease type 2
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
inherited
|
New York Genome Center
Accession: SCV004176035.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
Clinical Features:
Fatigue (present) , Migraine (present) , Chronic pain (present) , Joint laxity (present) , Joint dislocation (present) , Gastroparesis (present)
Secondary finding: no
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Pathogenic
(Nov 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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von Willebrand disease type 2
Affected status: yes
Allele origin:
germline
|
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV004244520.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
PS3, PM1, PM3_Strong
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Pathogenic
(Aug 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001246257.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Comment:
VWF: PP1:Strong, PM1, PM5, PS3:Moderate
Number of individuals with the variant: 11
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Pathogenic
(May 01, 2010)
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no assertion criteria provided
Method: literature only
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VON WILLEBRAND DISEASE, TYPE 2N
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000020464.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered … (more)
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ARG91GLN is now designated ARG854GLN (R854Q). In a patient with the Normandy type of von Willebrand disease (VWD2N; see 613554), Gaucher et al. (1991) demonstrated compound heterozygosity for the arg53-to-trp mutation (193400.0012) and another C-to-T transition that resulted in a substitution of glutamine for arginine-91. The patient's parents were related as second cousins. Hilbert et al. (2004) reported 2 unrelated French patients with type 2N VWD who were compound heterozygous for R854Q and another pathogenic mutation (Y795C, 613160.0031 and C804F, 613160.0032, respectively). Peerlinck et al. (1992) identified a heterozygous A-to-G transition in exon 20 of the VWF gene, resulting in an arg854-to-gln (R854Q) substitution, in a 23-year-old woman with a lifelong history of bleeding and low VWF levels, consistent with von Willebrand disease type 1 (193400). Laboratory studies showed disproportionately low factor VIII (F8; 300841) and decreased binding capacity of VWF for F8. The R854Q substitution occurred in the putative factor VIII-binding domain. All VWF multimers were normal. Neither parent was clinically affected, but laboratory studies showed that the father had partially increased bleeding time and partially decreased VWF antigen. Restriction enzyme analysis indicated that the unaffected mother was also heterozygous for the R854Q mutation, and that the patient had inherited a hypomorphic 'silent' VWF allele from her father. Peerlinck et al. (1992) noted that the inheritance pattern in this family was difficult to determine, but concluded that the presence of the 'silent' allele allowed the clinical expression of the mutated second allele, resulting in a recessive phenotype in the proband. Peerlinck et al. (1992) commented that although the phenotype was similar to that of the 'Normandy' type 2N variant (see 613554), the patient also had quantitatively low VWF and was thus classified as having VWD type 1. (less)
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Pathogenic
(May 01, 2010)
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no assertion criteria provided
Method: literature only
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VON WILLEBRAND DISEASE, TYPE 1
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000020465.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered … (more)
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ARG91GLN is now designated ARG854GLN (R854Q). In a patient with the Normandy type of von Willebrand disease (VWD2N; see 613554), Gaucher et al. (1991) demonstrated compound heterozygosity for the arg53-to-trp mutation (193400.0012) and another C-to-T transition that resulted in a substitution of glutamine for arginine-91. The patient's parents were related as second cousins. Hilbert et al. (2004) reported 2 unrelated French patients with type 2N VWD who were compound heterozygous for R854Q and another pathogenic mutation (Y795C, 613160.0031 and C804F, 613160.0032, respectively). Peerlinck et al. (1992) identified a heterozygous A-to-G transition in exon 20 of the VWF gene, resulting in an arg854-to-gln (R854Q) substitution, in a 23-year-old woman with a lifelong history of bleeding and low VWF levels, consistent with von Willebrand disease type 1 (193400). Laboratory studies showed disproportionately low factor VIII (F8; 300841) and decreased binding capacity of VWF for F8. The R854Q substitution occurred in the putative factor VIII-binding domain. All VWF multimers were normal. Neither parent was clinically affected, but laboratory studies showed that the father had partially increased bleeding time and partially decreased VWF antigen. Restriction enzyme analysis indicated that the unaffected mother was also heterozygous for the R854Q mutation, and that the patient had inherited a hypomorphic 'silent' VWF allele from her father. Peerlinck et al. (1992) noted that the inheritance pattern in this family was difficult to determine, but concluded that the presence of the 'silent' allele allowed the clinical expression of the mutated second allele, resulting in a recessive phenotype in the proband. Peerlinck et al. (1992) commented that although the phenotype was similar to that of the 'Normandy' type 2N variant (see 613554), the patient also had quantitatively low VWF and was thus classified as having VWD type 1. (less)
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Pathogenic
(Jan 06, 2020)
|
no assertion criteria provided
Method: curation
|
von Willebrand disease, type 1
Affected status: unknown
Allele origin:
germline
|
Reproductive Health Research and Development, BGI Genomics
Accession: SCV001142429.1
First in ClinVar: Jan 12, 2020 Last updated: Jan 12, 2020 |
Comment:
NM_000552.3:c.2561G>A in the VWF gene has an allele frequency of 0.006 in European (Finnish) subpopulation in the gnomAD database. The p.Arg854Gln (NM_000552.3:c.2561G>A) variant in the … (more)
NM_000552.3:c.2561G>A in the VWF gene has an allele frequency of 0.006 in European (Finnish) subpopulation in the gnomAD database. The p.Arg854Gln (NM_000552.3:c.2561G>A) variant in the VWF gene is the most frequent cause of von Willebrand disease (VWD) type 2N and has been reported previously in the homozygous state or in trans with another pathogenic variant in multiple unrelated individuals with autosomal recessive VWD type 2N (PMID: 1832934; 21371195; 15461624). Functional studies indicate the p.Arg854Gln variant may affect protein function (PMID: 23636243; 23426949). Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP Criteria applied: PM3_Strong; PS3; PP4. (less)
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001552634.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The VWF p.R854Q variant was identified in multiple homozygous or compound heterozygous individuals with autosomal recessive Von Willebrand disease (VWD) type 2N (Casonato_2016_PMID:27532107; Casonato_2007_PMID:17456630; Rodgers_2002_PMID:12162689; … (more)
The VWF p.R854Q variant was identified in multiple homozygous or compound heterozygous individuals with autosomal recessive Von Willebrand disease (VWD) type 2N (Casonato_2016_PMID:27532107; Casonato_2007_PMID:17456630; Rodgers_2002_PMID:12162689; Cabrera_2008_PMID:18712522). In one family study, two sisters with borderline VWD type 2N were compound heterozygotes for this variant and p.Q895H; the father and mother were asymptomatic carriers for p.Q895H and p.R854Q, respectively (Cabrera_2008_PMID:18712522). The variant was identified in dbSNP (ID: rs41276738) and ClinVar (classified as pathogenic by Laboratory for Molecular Medicine, GeneDx and 11 other laboratories). The variant was identified in control databases in 980 of 282824 chromosomes (5 homozygous) at a frequency of 0.003465 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (Finnish) in 143 of 25122 chromosomes (freq: 0.005692), European (non-Finnish) in 690 of 129142 chromosomes (freq: 0.005343), Other in 26 of 7226 chromosomes (freq: 0.003598), Latino in 74 of 35428 chromosomes (freq: 0.002089), Ashkenazi Jewish in 10 of 10370 chromosomes (freq: 0.000964), African in 21 of 24968 chromosomes (freq: 0.000841) and South Asian in 16 of 30614 chromosomes (freq: 0.000523), but was not observed in the East Asian population. The p.Arg854 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein. The VWF gene encodes Von Willebrand factor, which interacts with coagulation factor VIII (FVIII) for hemostasis. Functional studies reveal that this variant causes significantly decreased binding between VMF and FVIII compared to wild type (Kroner_1991_PMID:1918030; Rosenberg_2002_PMID:12176890; Dagil_2019_PMID: 31349985). The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing and the creation of a new 3' splice site. However, this has not been confirmed by RNA analysis. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001740446.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001954827.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Likely pathogenic
(May 01, 2020)
|
no assertion criteria provided
Method: research
|
Thrombocytopenia
Abnormal bleeding
Affected status: yes
Allele origin:
germline
|
Birmingham Platelet Group; University of Birmingham
Accession: SCV001450828.1
First in ClinVar: Dec 19, 2020 Last updated: Dec 19, 2020 |
|
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808213.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001965898.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Uncertain significance
(Apr 26, 2022)
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no assertion criteria provided
Method: clinical testing
|
von Willebrand disease type 2
Affected status: yes
Allele origin:
germline
|
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Accession: SCV002513416.1
First in ClinVar: May 21, 2022 Last updated: May 21, 2022 |
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not provided
(-)
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no classification provided
Method: literature only
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von Willebrand disorder
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV002507237.2
First in ClinVar: May 16, 2022 Last updated: Oct 01, 2022 |
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not provided
(-)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
not provided
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Academic Unit of Haematology, University of Sheffield
Accession: SCV000118824.1
First in ClinVar: Feb 21, 2014 Last updated: Feb 21, 2014 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
GoldVariants, a resource for sharing rare genetic variants detected in bleeding, thrombotic, and platelet disorders: Communication from the ISTH SSC Subcommittee on Genomics in Thrombosis and Hemostasis. | Megy K | Journal of thrombosis and haemostasis : JTH | 2021 | PMID: 34355501 |
Interaction Between the a3 Region of Factor VIII and the TIL'E' Domains of the von Willebrand Factor. | Dagil L | Biophysical journal | 2019 | PMID: 31349985 |
Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders. | Downes K | Blood | 2019 | PMID: 31064749 |
Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients. | Borràs N | Haematologica | 2017 | PMID: 28971901 |
Abnormal von Willebrand factor secretion, factor VIII stabilization and thrombus dynamics in type 2N von Willebrand disease mice. | Swystun LL | Journal of thrombosis and haemostasis : JTH | 2017 | PMID: 28581694 |
von Willebrand Disease. | Adam MP | - | 2017 | PMID: 20301765 |
Genotype-phenotype correlation in a cohort of Portuguese patients comprising the entire spectrum of VWD types: impact of NGS. | Fidalgo T | Thrombosis and haemostasis | 2016 | PMID: 26988807 |
267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation. | Dopazo J | Molecular biology and evolution | 2016 | PMID: 26764160 |
Clinical phenotype in genetically confirmed von Willebrand disease type 2N patients reflects a haemophilia A phenotype. | van Meegeren ME | Haemophilia : the official journal of the World Federation of Hemophilia | 2015 | PMID: 26207643 |
von Willebrand factor, Jedi knight of the bloodstream. | Springer TA | Blood | 2014 | PMID: 24928861 |
Comprehensive genetic analysis of complement and coagulation genes in atypical hemolytic uremic syndrome. | Bu F | Journal of the American Society of Nephrology : JASN | 2014 | PMID: 24029428 |
Compromised shear-dependent cleavage of type 2N von Willebrand factor variants by ADAMTS13 in the presence of factor VIII. | Skipwith CG | Thrombosis and haemostasis | 2013 | PMID: 23636243 |
Analysis of the storage and secretion of von Willebrand factor in blood outgrowth endothelial cells derived from patients with von Willebrand disease. | Wang JW | Blood | 2013 | PMID: 23426949 |
A common ancestor more than 10,000 years old for patients with R854Q-related type 2N von Willebrand's disease in Italy. | Casonato A | Haematologica | 2013 | PMID: 22875612 |
VWF mutations and new sequence variations identified in healthy controls are more frequent in the African-American population. | Bellissimo DB | Blood | 2012 | PMID: 22197721 |
Validation of the first commercial ELISA for type 2N von Willebrand's disease diagnosis. | Veyradier A | Haemophilia : the official journal of the World Federation of Hemophilia | 2011 | PMID: 21371195 |
A map of human genome variation from population-scale sequencing. | 1000 Genomes Project Consortium | Nature | 2010 | PMID: 20981092 |
Homozygous type 2N R854W von Willebrand factor is poorly secreted and causes a severe von Willebrand disease phenotype. | Castaman G | Journal of thrombosis and haemostasis : JTH | 2010 | PMID: 20586924 |
The genetic basis of von Willebrand disease. | Goodeve AC | Blood reviews | 2010 | PMID: 20409624 |
Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD). | Goodeve A | Blood | 2007 | PMID: 16985174 |
Type 2N von Willebrand disease due to compound heterozygosity for R854Q and a novel R763G mutation at the cleavage site of von Willebrand factor propeptide. | Hilbert L | Thrombosis and haemostasis | 2006 | PMID: 16953269 |
A practical approach to genetic testing for von Willebrand disease. | Pruthi RK | Mayo Clinic proceedings | 2006 | PMID: 16706266 |
Pregnancy and delivery in patients with homozygous or heterozygous R854Q type 2N von Willebrand disease. | Castaman G | Journal of thrombosis and haemostasis : JTH | 2005 | PMID: 15670054 |
Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene. | Hilbert L | British journal of haematology | 2004 | PMID: 15461624 |
First Italian families with homozygous R854Q type 2 N von Willebrand disease. | Castaman G | Thrombosis and haemostasis | 2002 | PMID: 12353087 |
ABO blood group also influences the von Willebrand factor (VWF) antigen level in heterozygous carriers of VWF null alleles, type 2N mutation Arg854GIn, and the missense mutation Cys2362Phe. | Castaman G | Blood | 2002 | PMID: 12211196 |
The role of the D1 domain of the von Willebrand factor propeptide in multimerization of VWF. | Rosenberg JB | Blood | 2002 | PMID: 12176890 |
Type 2N von Willebrand disease: clinical manifestations, pathophysiology, laboratory diagnosis and molecular biology. | Mazurier C | Best practice & research. Clinical haematology | 2001 | PMID: 11686103 |
Type 2N von Willebrand disease: rapid genetic diagnosis of G2811A (R854Q), C2696T (R816W), T2701A (H817Q) and G2823T (C858F)--detection of a novel candidate type 2N mutation: C2810T (R854W). | Bowen DJ | Thrombosis and haemostasis | 1998 | PMID: 9684781 |
Factor VIII binding assay of von Willebrand factor and the diagnosis of type 2N von Willebrand disease--results of an international survey. On behalf of the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the ISTH. | Mazurier C | Thrombosis and haemostasis | 1996 | PMID: 8865544 |
Autosomal recessive transmission of hemophilia A due to a von Willebrand factor mutation. | Wise RJ | Human genetics | 1993 | PMID: 8500791 |
A patient with von Willebrand's disease characterized by a compound heterozygosity for a substitution of Arg854 by Gln in the putative factor-VIII-binding domain of von Willebrand factor (vWF) on one allele and very low levels of mRNA from the second vWF allele. | Peerlinck K | British journal of haematology | 1992 | PMID: 1581215 |
Abnormal binding of factor VIII is linked with the substitution of glutamine for arginine 91 in von Willebrand factor in a variant form of von Willebrand disease. | Kroner PA | The Journal of biological chemistry | 1991 | PMID: 1918030 |
Molecular characterization of a unique von Willebrand disease variant. A novel mutation affecting von Willebrand factor/factor VIII interaction. | Cacheris PM | The Journal of biological chemistry | 1991 | PMID: 1906877 |
Identification of two point mutations in the von Willebrand factor gene of three families with the 'Normandy' variant of von Willebrand disease. | Gaucher C | British journal of haematology | 1991 | PMID: 1832934 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=VWF | - | - | - | - |
http://www.vwf.group.shef.ac.uk/ | - | - | - | - |
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Text-mined citations for rs41276738 ...
HelpRecord last updated May 12, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.