Genes in panel
Regions in panel
Prev Next

Intellectual disability

Gene: VPS53

Green List (high evidence)

VPS53 (VPS53, GARP complex subunit)
EnsemblGeneIds (GRCh38): ENSG00000141252
EnsemblGeneIds (GRCh37): ENSG00000141252
OMIM: 615850, Gene2Phenotype
VPS53 is in 10 panels

2 reviews

Louise Daugherty (Genomics England Curator)

Comment on list classification: After internal clinical review it was decided that this gene could be rated Green. Even though there is a founder effect in this population, there is further evidence for it being the gene of interest by the fact that there is more than one variant identified. There are 4 unrelated families and two variants.
Created: 20 Jul 2018, 11:49 a.m.
Comment on phenotypes: added phenotypes to support gene on ID panel . All 10 patients of the four apparently unrelated non-consanguineous Jewish Moroccan families had profound mental retardation, gaining practically no developmental milestones except visual tracking and smiling.
Created: 16 Jul 2018, 1:59 p.m.
Comment on list classification: New Amber gene added by external expert review, publications support gene-disease association and noted from literature and review this is a founder-effect gene. Referred to internal clinical to consider rating Green review due to presence of missense and splice site variants
Created: 16 Jul 2018, 1:51 p.m.
added founder-effect tag
Created: 16 Jul 2018, 1:46 p.m.
It was noted by Feinstein et al. (2014) that the variants segregated with the disorder in the families. The Q695R substitution occured at a highly conserved residue in the second helix of the surface of the C terminus. Study of patient lymphocytes suggested that the splice site mutation was either subject to nonsense-mediated mRNA decay or resulted in a truncated protein. Of Jewish Moroccan controls tested, 2 of 143 carried the missense mutation and 2 of 156 carried the splice site mutation, yielding a carrier frequency of 1 in 37 for each of the mutations in this population, consistent with a founder effect
Created: 16 Jul 2018, 1:44 p.m.
Comment on publications: PMID:24577744. In 10 affected individuals from 4 nonconsanguineous families of Jewish Moroccan descent with pontocerebellar hypoplasia type 2E (PCH2E; 615851), Feinstein et al. (2014) identified two compound heterozygous mutations in the VPS53 gene. NM_001128159.2(VPS53):c.2084A>G (p.Gln695Arg) and NM_001128159.2(VPS53):c.1556+5G>A
Created: 16 Jul 2018, 1:36 p.m.
Comment on phenotypes: added omim MIMid and Orphanet phenotype
Created: 16 Jul 2018, 1:31 p.m.

Zornitza Stark (Australian Genomics)

I don't know

10 individuals from 4 families reported in the literature with bi-allelic variants, but ?founder effect. Consider inclusion as Amber if not Green.
Created: 22 Jun 2018, 3:05 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pontocerebellar hypoplasia, type 2E

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
Phenotypes
  • Pontocerebellar hypoplasia, type 2E, 615851
  • Progressive cerebello-cerebral atrophy
  • intellectual disability
  • developmental delay
Tags
founder-effect
OMIM
615850
Clinvar variants
Variants in VPS53
Penetrance
None
Publications
Panels with this gene

History Filter Activity

29 Sep 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to VPS53.

20 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: vps53 has been classified as Green List (High Evidence).

16 Jul 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: VPS53 were set to Pontocerebellar hypoplasia, type 2E, 615851; Progressive cerebello-cerebral atrophy; intellectual disability; developmental delay

16 Jul 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: vps53 has been classified as Amber List (Moderate Evidence).

16 Jul 2018, Gel status: 0

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: VPS53 were set to 24577744; 2920088

16 Jul 2018, Gel status: 0

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: VPS53 were set to Pontocerebellar hypoplasia, type 2E, 615851; Progressive cerebello-cerebral atrophy

22 Jun 2018, Gel status: 0

Added New Source

Zornitza Stark (Australian Genomics)

VPS53 was added to Intellectual disability panel. Sources: Literature

22 Jun 2018, Gel status: 0

Created

Zornitza Stark (Australian Genomics)

VPS53 was created by Zornitza Stark