Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000551.4(VHL):c.477del (p.Glu160fs)

CA020404

182959 (ClinVar)

Gene: VHL

Condition: von Hippel-Lindau disease

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

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

Pathogenic

PM2_Supporting PVS1 PS4_Moderate

Evidence Links 0

Expert Panel

VHL VCEP

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).

PM2_Supporting

This variant is absent from gnomAD v4.1.0 (PM2_Supporting).

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).

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).

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