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Hereditary neuropathy NOT PMP22 copy number

Gene: VCP

Amber List (moderate evidence)

VCP (valosin containing protein)
EnsemblGeneIds (GRCh38): ENSG00000165280
EnsemblGeneIds (GRCh37): ENSG00000165280
OMIM: 601023, Gene2Phenotype
VCP is in 11 panels

6 reviews

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Third family reported with phenotypic variability between the proband, his brother, and father. - The clinical diagnosis of CMT2 was based on the observations of distal amyotrophy and mild sensory abnormalities, and electrophysiological evidence of chronic progressive axonopathy in the proband. - The proband's brother had fewer clinical signs of CMT2 compared to the proband and his father, with mild hand weakness and length-dependent sensory deficits with no lower extremity weakness. - The findings in the father reflected a novel phenotypic partial synthesis of ALS-like (i.e., UMN and LMN) in conjunction with CMT2-like (motor and sensory) phenomena.
Created: 9 Aug 2021, 10:58 a.m. | Last Modified: 9 Aug 2021, 10:58 a.m.
Panel Version: 1.37

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Charcot-Marie-Tooth disease, type 2Y, MIM# 616687

Publications

Mode of pathogenicity
Other

Alexander Rossor (UCL Institute of Neurology)

Only two families reported, unclear if definitely causes CMT
Created: 9 May 2019, 12:12 p.m.

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Downgraded from Green to Amber from recommendation from Alex Rossor - only two published cases of VCP and neuropathy. P.Glu185Lys is absent form GNOMAD but p.Glu185Asp is present 4 times. I don’t think there have been any more cases. Might it be better as Amber for neuropathy?
Created: 13 Dec 2019, 1:36 p.m. | Last Modified: 13 Dec 2019, 1:36 p.m.
Panel Version: 0.106
Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - minor feature / Broader phenotype: ALS+/-FTD; unclear whether also causes CMT - Amber? Very rare but I think include as Green as reasonable evidence for distal myopathy/neuropathy
Created: 7 Dec 2019, 12:03 a.m. | Last Modified: 7 Dec 2019, 12:03 a.m.
Panel Version: 0.86
This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Created: 6 Dec 2019, 10:25 p.m. | Last Modified: 6 Dec 2019, 10:25 p.m.
Panel Version: 0.84
Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.
Created: 11 Jun 2019, 1:40 p.m.
Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 5 p.m.

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Red List (low evidence)

Two families
Created: 29 Apr 2019, 9:20 a.m.

Variants in this GENE are reported as part of current diagnostic practice

Mary Reilly (Institute of Neurology)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Ellen McDonagh (Genomics England Curator)

Is on the Charcot-Marie- Tooth disease type 2 / Intermediate CMT NGS Panel in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual.
Created: 10 Jun 2016, 1:10 p.m.
Comment on list classification: Gene added by a reviewer, and rated green by a second reviewer.
Created: 9 May 2016, 10:10 a.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Expert Review
  • London North GLH
  • NHS GMS
  • NHS GMS
  • London North GLH
Phenotypes
  • Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia
  • Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1
  • Charcot-Marie-Tooth disease, type 2Y
OMIM
601023
Clinvar variants
Variants in VCP
Penetrance
None
Publications
Panels with this gene

History Filter Activity

13 Dec 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: vcp has been classified as Amber List (Moderate Evidence).

7 Dec 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: vcp has been classified as Green List (High Evidence).

6 Dec 2019, Gel status: 2

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Amber was added to VCP. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)

5 Dec 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ellen McDonagh (Genomics England Curator)

gene: VCP was added gene: VCP was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH,Expert Review,Expert Review Green Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VCP were set to 26574898; 25878907; 25125609 Phenotypes for gene: VCP were set to Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia; Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1; Charcot-Marie-Tooth disease, type 2Y