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
  • Despite there being a valid 'cspec' property in the messages there's a discrepancy in message contents and CSPEC data: * Message Gene: VWF CSPEC Genes: [ 'VWF' ] * Message MONDOs: MONDO:0019565 CSPEC MONDO: [ 'MONDO:0015628', 'MONDO:0015629', 'MONDO:0015630', 'MONDO:0013304', 'MONDO:0024574' ]
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000552.5(VWF):c.114C>T (p.Phe38=)

CA6403892

310090 (ClinVar)

Gene: VWF (HGNC:7450)
Condition: hereditary von Willebrand disease (MONDO:0019565)
Inheritance Mode: Undetermined mode of inheritance
UUID: cfd48011-0567-4737-89f3-94111d00add9
Approved on: 2025-11-04
Published on: 2025-11-04

HGVS expressions

NM_000552.5:c.114C>T
NM_000552.5(VWF):c.114C>T (p.Phe38=)
NC_000012.12:g.6121280G>A
CM000674.2:g.6121280G>A
NC_000012.11:g.6230446G>A
CM000674.1:g.6230446G>A
NC_000012.10:g.6100707G>A
NG_009072.1:g.8391C>T
NG_009072.2:g.8391C>T
ENST00000261405.10:c.114C>T
ENST00000261405.9:c.114C>T
ENST00000321023.5:c.*173C>T
ENST00000538563.1:c.*173C>T
ENST00000538635.5:n.143C>T
NM_000552.3:c.114C>T
NM_000552.4:c.114C>T
More

Likely Benign

Met criteria codes 2
BP7 BP4
Not Met criteria codes 2
BP5 BS1

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_000552.5:c.114C>T (p.Phe38=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing (BP4 & BP7). A case carrying the c.114C>T (p.Phe38=) variant was also found to carry the ClinGen VWD VCEP curated pathogenic variant c.2435del. The case is asserted to be VWD 3 which is typically a biallelic variant but there is not a second variant in this case curated pathogenic (PMID 16321553). Additionally, there are 8 submissions to ClinVar for this variant but for the submissions indicating affected status as yes, all classify the variant as likely benign. In summary, this variant meets the criteria to be classified as likely benign for hereditary von Willebrand disease based on the ACMG/AMP criteria applied, as specified by the ClinGen VWD VCEP: BP4, BP7 (VWD VCEP specifications v1l)
Met criteria codes
BP7
The c.114C>T (p.Phe38=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing (BP7).
BP4
The c.114C>T (p.Phe38=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing (BP4).
Not Met criteria codes
BP5
A case carrying the c.114C>T (p.Phe38=) variant was also found to carry the ClinGen VWD VCEP curated pathogenic variant c.2435del. The case is asserted to be VWD 3 which is typically a biallelic variant but there is not a second variant in this case curated pathogenic (PMID 16321553).
BS1
The Grpmax filtering allele frequency in gnomAD v4.1 is 0.004699 (based on 5669/1180026 alleles in the European non Finnish population, and 19 homozygotes). This intermediate allele frequency is lower than the ClinGen VWD VCEP threshold (>0.01) for BS1 but higher than the threshold (<0.0001 for type 2) for PM2_Supporting.
Curation History
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