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_000551.4(VHL):c.477del (p.Glu160fs)

CA020404

182959 (ClinVar)

Gene: VHL
Condition: von Hippel-Lindau disease
Inheritance Mode: Autosomal dominant inheritance
UUID: 45d26de0-d6f0-438e-b530-8ee7a1cd8668
Approved on: 2024-06-25
Published on: 2024-06-25

HGVS expressions

NM_000551.4:c.477del
NM_000551.4(VHL):c.477del (p.Glu160fs)
NC_000003.12:g.10149800del
CM000665.2:g.10149800del
NC_000003.11:g.10191484del
CM000665.1:g.10191484del
NC_000003.10:g.10166484del
NG_008212.3:g.13166del
ENST00000696142.1:c.*154del
ENST00000696143.1:c.613del
ENST00000696153.1:c.588del
ENST00000256474.3:c.477del
ENST00000256474.2:c.477del
ENST00000345392.2:c.354del
ENST00000477538.1:n.613del
NM_000551.3:c.477del
NM_198156.2:c.354del
NM_001354723.1:c.*31del
NM_001354723.2:c.*31del
NM_198156.3:c.354del
More

Pathogenic

Met criteria codes 3
PVS1 PM2_Supporting PS4_Moderate

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen VHL Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for VHL Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
VHL VCEP
This variant has been identified in at least 9 unrelated probands (and other related family members not counted within each) all meeting Danish VHL criteria, from literature evaluated in both CIViC and Hypothes.is VHL datasets. CIViC EIDs (https://civicdb.org): 8292;7606;5776;9374;6806;6538. This corresponds to Strong evidence (5-15 probands) (PS4). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). This variant has been reported in 3 probands/families meeting meeting either VHL Type 1 or affected with VHL-related cancers. (2.25 points, PS4_Moderate; PMID: 11114638, 12114494, 9829911). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal-dominant von Hippel Lindau syndrome (VHL syndrome) based on the ACMG/AMP criteria applied, as specified by the ClinGen VHL VCEP Version 1.0 (Specifications approval date: 02/26/2024. Variant Approval Date 06/25/2024).
Met criteria codes
PVS1
The c.477del variant in VHL is a frameshift variant in a biologically relevant exon. It is not predicted to cause nonsense mediated decay but it is in a critical domain (alpha domain, elongin binding 157-172) of the protein (PVS1).
PM2_Supporting
This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
PS4_Moderate
This variant has been reported in 3 probands/families meeting meeting either VHL Type 1 or affected with VHL-related cancers. (2.25 points, PS4_Moderate; PMID: 11114638, 12114494, 9829911).
Curation History
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