NM_000552.5(VWF):c.6937C>T (p.Arg2313Cys) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jan 23, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001284740.7

Allele description [Variation Report for NM_000552.5(VWF):c.6937C>T (p.Arg2313Cys)]

NM_000552.5(VWF):c.6937C>T (p.Arg2313Cys)

Gene:

VWF:von Willebrand factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p13.31

Genomic location:

Preferred name:

NM_000552.5(VWF):c.6937C>T (p.Arg2313Cys)

Other names:

p.Arg2313Cys

HGVS:

NC_000012.12:g.5985084G>A
NG_009072.2:g.144587C>T
NM_000552.5:c.6937C>TMANE SELECT
NP_000543.3:p.Arg2313Cys
LRG_587t1:c.6937C>T
LRG_587:g.144587C>T
LRG_587p1:p.Arg2313Cys
NC_000012.11:g.6094250G>A
NG_009072.1:g.144587C>T
NM_000552.3:c.6937C>T
NM_000552.4:c.6937C>T

Protein change:

R2313C

Links:

dbSNP: rs184921605

NCBI 1000 Genomes Browser:

rs184921605

Molecular consequence:

NM_000552.5:c.6937C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001470688	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jul 20, 2023)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25780857, 23216583, 26467025
SCV003799292	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021)	Uncertain significance (May 27, 2022)	germline	clinical testing	Citation Link,
SCV005408216	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 23, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25780857, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001470688

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jul 20, 2023)

unknown

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV003799292

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)

Uncertain significance
(May 27, 2022)

germline

clinical testing

Citation Link,

SCV005408216

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 23, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Characterizing polymorphisms and allelic diversity of von Willebrand factor gene in the 1000 Genomes.

Wang QY, Song J, Gibbs RA, Boerwinkle E, Dong JF, Yu FL.

J Thromb Haemost. 2013 Feb;11(2):261-9. doi: 10.1111/jth.12093.

PubMed [citation]

PMID:: 23216583
PMCID:: PMC3570679

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

See all PubMed Citations (4)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001470688.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In the published literature, the variant has been reported in an individual with hemophilia A (HA) who exhibited low plasma VWF antigen (VWF:Ag) and Factor VIII (FVIII) binding capacities (PMID: 25780857 (2015)). The frequency of this variant in the general population, 0.003 (75/24960 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Taking into account the available information, we are unable to determine the clinical significance of this variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV003799292.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The VWF c.6937C>T; p.Arg2313Cys variant (rs184921605) is reported in the literature in an individual with low von Willebrand factor (Boylan 2015). This variant is also reported in ClinVar (Variation ID: 993252). This variant is found in the Latino population with an allele frequency of 0.6 % (234/ 35,440 alleles, including 0 homozygotes) in the Genome Aggregation Database. The arginine at codon 2313 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.29). Due to limited information, the clinical significance of the p.Arg2313Cys variant is uncertain at this time.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV005408216.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (2)

Description

PM1

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		2	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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