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Intellectual disability

Gene: VPS11

Amber List (moderate evidence)

VPS11 (VPS11, CORVET/HOPS core subunit)
EnsemblGeneIds (GRCh38): ENSG00000160695
EnsemblGeneIds (GRCh37): ENSG00000160695
OMIM: 608549, Gene2Phenotype
VPS11 is in 4 panels

2 reviews

Catherine Snow (Genomics England)

Comment on list classification: Gene identified by an expert review by Konstantinos Varvagiannis. Although Konstantinos Varvagiannis suggests that this should be green. PMIDs: 27120463 and 26307567 report on 13 individuals from 7 Ashkenazi families, all with the same variant, therefore reported as a founder effect. A second variant (p.Leu387_Gly395del) was however found in the homozygous state in 2 sibs born to consanguineous parents of a Turkish origin (PMID: 27473128). VPS11 is in OMIM and ID phenotype is relevant.
However as only two unique variants have been identified so far, classifying VPS11 as Amber and adding to the watch list.
Created: 28 May 2019, 9:48 a.m. | Last Modified: 25 Jun 2019, 3:05 p.m.
Panel Version: 0.194

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Biallelic mutations in VPS11 cause Leukodystrophy, hypomyelinating, 12 (MIM 616683).

PMIDs: 27120463, 26307567, 27473128 all report on this disorder.

The phenotype consists of global DD, ID, (variable) acquired microcephaly with hypomyelination upon brain MRI. Seizures appear to be a feature in several individuals.

Almost all individuals appear to be of Ashkenazi Jewish descent, homozygous for a founder mutation (NM_021729.5:c.2536T>G or p.Cys846Gly). PMIDs: 27120463 and 26307567 report on 13 individuals from 7 Ashkenazi families.

A second variant (p.Leu387_Gly395del) was however found in the homozygous state in 2 sibs born to consanguineous parents.

Pathogenicity is supported by extensive functional studies in all relevant articles.

VPS11 is not associated with any phenotype in G2P.

The gene is included in gene panels for ID offered by diagnostic laboratories (incl. Radboudumc).

As a result, this gene can be considered for inclusion in this panel as green.

[Please consider inclusion in the lysosomal disorders panel as well as in the undiagnosed metabolic disorders panel].
Sources: Literature, Radboud University Medical Center, Nijmegen
Created: 14 Dec 2018, 4:02 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating, 12 (MIM 616683)

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Expert Review
  • Expert Review Amber
  • Expert Review
Phenotypes
  • Leukodystrophy, hypomyelinating, 12, 616683
  • Leukodystrophy, hypomyelinating, 12 (MIM 616683)
Tags
watchlist
OMIM
608549
Clinvar variants
Variants in VPS11
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

25 Jul 2019, Gel status: 2

Added Tag

Catherine Snow (Genomics England)

Tag watchlist tag was added to gene: VPS11.

25 Jul 2019, Gel status: 2

Added New Source, Added New Source, Set Phenotypes, Set publications, Status Update

Catherine Snow (Genomics England)

Source Expert Review was added to VPS11. Source Expert Review Amber was added to VPS11. Added phenotypes Leukodystrophy, hypomyelinating, 12, 616683 for gene: VPS11 Publications for gene VPS11 were changed from 27120463; 26307567; 27473128 to 27473128; 26307567; 27120463 Rating Changed from No List (delete) to Amber List (moderate evidence)

14 Dec 2018, Gel status: 0

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

Konstantinos Varvagiannis (Other)

gene: VPS11 was added gene: VPS11 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: VPS11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS11 were set to 27120463; 26307567; 27473128 Phenotypes for gene: VPS11 were set to Leukodystrophy, hypomyelinating, 12 (MIM 616683) Penetrance for gene: VPS11 were set to Complete Review for gene: VPS11 was set to GREEN gene: VPS11 was marked as current diagnostic