Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_000552.5(VWF):c.8113G>A (p.Gly2705Arg)

CA6401404

256702 (ClinVar)

Gene: VWF
Condition: hereditary von Willebrand disease
Inheritance Mode: Undetermined mode of inheritance
Link to MONDO
UUID: 3b275b80-2d99-4211-9e2b-dd6792e87864
Approved on: 2024-08-13
Published on: 2024-08-13

HGVS expressions

NM_000552.5:c.8113G>A
NM_000552.5(VWF):c.8113G>A (p.Gly2705Arg)
NC_000012.12:g.5952393C>T
CM000674.2:g.5952393C>T
NC_000012.11:g.6061559C>T
CM000674.1:g.6061559C>T
NC_000012.10:g.5931820C>T
NG_009072.1:g.177278G>A
NG_009072.2:g.177278G>A
ENST00000261405.10:c.8113G>A
ENST00000261405.9:c.8113G>A
ENST00000612016.1:n.522G>A
ENST00000621700.1:n.431G>A
NM_000552.3:c.8113G>A
NM_000552.4:c.8113G>A
More

Benign

Met criteria codes 1
BA1
Not Met criteria codes 3
PP4 PP3 BP4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen von Willebrand Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for VWF Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
von Willebrand Disease VCEP
The NM_000552.4(VWF):c.8113G>A (p.Gly2705Arg) variant in VWF is a missense variant predicted to cause substitution of Glycine by Arginine at amino acid 2705. The Grpmax filtering allele frequency in gnomAD v4.1 is 0.1227 (based on 11352/91062 alleles in the South Asian population, including 829 homozygotes), which is higher than the ClinGen VWD VCEP threshold of >0.1 for BA1. As reported in PMID: 26105150 the variant is significantly associated with lower plasma levels of FVIII but not vWF. In summary this variant is classified as Benign for VWD based on the ACMG/AMP criteria applied, as specified by the ClinGen VWD VCEP: BA1
Met criteria codes
BA1
The Grpmax filtering allele frequency in gnomAD v4.1 is 0.1227 (based on 11352/91062 alleles in the South Asian population, including 829 homozygotes), which is higher than the ClinGen VWD VCEP threshold of >0.1 for BA1.
Not Met criteria codes
PP4
As reported in PMID: 26105150 the variant is significantly associated with lower plasma levels of FVIII but not vWF.
PP3
The computational predictor REVEL gives a score of 0.294, which is below the ClinGen VWD VCEP PP3 threshold of >0.644 and does not predict a damaging effect on VWF function. SpliceAI does not strongly predict a splicing effect (delta score for donor loss of only 0.01 at pre-mRNA position of -6 bp, which falls below the confident prediction threshold of ≥0.5).
BP4
The computational predictor REVEL gives a score of 0.294, which is above the ClinGen VWD VCEP threshold of <0.290.
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.