Malformations of cortical development

Gene: TUBA8

Amber List (moderate evidence)

TUBA8 (tubulin alpha 8)
EnsemblGeneIds (GRCh38): ENSG00000183785
EnsemblGeneIds (GRCh37): ENSG00000183785
OMIM: 605742, Gene2Phenotype
TUBA8 is in 12 panels

3 reviews

Rebecca Foulger (Genomics England curator)

Comment on list classification: Demoted from Green to Amber based on re-review of evidence. Demotion was agreed by Clinical Fellow Helen Brittain.

TUBA8 was originally rated Green on the panel because TUBA8 is a confirmed DD-G2P gene for 'POLYMICROGYRIA WITH OPTIC NERVE HYPOPLASIA' (the former name for Cortical dysplasia, complex, with other brain malformations 8, 613180) and TUBA8 is on the UKGTN 43 gene panel for brain malformations:
https://ukgtn.nhs.uk/find-a-test/search-by-disorder-gene/brain-malformation-disorders-cortical-43-gene-panel-886/.

However, the reported evidence comes from one 2009 paper (PMID:19896110) with 4 literature cases coming from 2 consaguineous families (1 variant); at least PMID:25008804 questions whether the families are related. A 2017 paper identifies an additional VUS (compound heterozygous) in a chinese EE patient (PMID:29588952).

Anna de Burca confirmed that there are lots of cases with CNVs involving TUBA8 in DECIPHER but there are only two cases with SNVs in the gene. One of them is classified as unknown pathogenicity, the other likely benign.

I contacted Usha Kini at Oxford, and also the Leeds and Cardiff genetic testing groups (as recommended by Usha) since they all offer cortical malformation panels. All three confirmed (pers. comm. via email) that they have no further cases for TUBA8.

The literature evidence and communications from Oxford, Leeds and Cardiff all support demotion of TUBA8 to Amber rating: The phenotype is still appropriate for the panel but insufficient cases for diagnostic rating.

Added 'watchlist' tag to look out for further cases.
Created: 5 Nov 2018, 9:22 a.m.
Comment on mode of inheritance: Biallelic MOI supported by OMIM and DD-Gene2Phenotype.
Created: 5 Nov 2018, 9:20 a.m.

Alice Gardham (Genomics England)

Comment when marking as ready: Recognised on G2P
Created: 19 Dec 2016, 10:30 a.m.

Usha Kini (Oxford Centre for Genomic Medicine)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • Polymicrogyria with optic nerve hypoplasia 613180
Tags
watchlist
OMIM
605742
Clinvar variants
Variants in TUBA8
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

5 Nov 2018, Gel status: 2

Added Tag

Rebecca Foulger (Genomics England curator)

Tag watchlist tag was added to gene: TUBA8.

5 Nov 2018, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: tuba8 has been classified as Amber List (Moderate Evidence).

5 Nov 2018, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: TUBA8 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

19 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Alice Gardham (Genomics England)

This gene has been classified as Green List (High Evidence).

19 Dec 2016, Gel status: 3

Set Phenotypes

Alice Gardham (Genomics England)

Phenotypes for TUBA8 were set to Polymicrogyria with optic nerve hypoplasia 613180

19 Dec 2016, Gel status: 3

Set publications

Alice Gardham (Genomics England)

Publications for TUBA8 were set to 19896110

19 Dec 2016, Gel status: 3

Upload gene information

Alice Gardham (Genomics England)

TUBA8 was added to Malformations of cortical developmentpanel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen

22 Nov 2016, Gel status: 1

panel promoted to version 1

Sarah Leigh (Genomics England Curator)

Promoted to Version 1 on 22nd November 2016

11 May 2016, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

TUBA8 was added to Malformations of cortical developmentpanel. Sources: UKGTN

11 May 2016, Gel status: 0

Created

Sarah Leigh (Genomics England Curator)

TUBA8 was created by sleigh