Genes in panel

Ataxia and cerebellar anomalies - narrow panel

Gene: TMEM106B

Amber List (moderate evidence)

TMEM106B (transmembrane protein 106B)
EnsemblGeneIds (GRCh38): ENSG00000106460
EnsemblGeneIds (GRCh37): ENSG00000106460
OMIM: 613413, Gene2Phenotype
TMEM106B is in 6 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

I don't know

Comment on list classification: Rating Amber as only 2/6 cases present ataxia, which is mild in one individual. Cases are more likely to be recognised for the leukodystrophy feature of this disease presentation; however, this may be reviewed if evidence emerges of a more prominent ataxic phenotype.
Created: 12 Nov 2020, 5:16 p.m. | Last Modified: 12 Nov 2020, 5:16 p.m.
Panel Version: 2.25
Associated with relevant phenotype in OMIM, and is a 'probable' gene for 'TMEM106B related hypomyelinating leukodystrophy' in Gene2Phenotype.

Recurrent variant c.754G>A p.(Asp252Asn) identified in 6 unrelated families from different ethnicities. Clinical characteristics include hypomyelinating leukodystrophy (6/6), nystagmus (6/6), hypotonia (5/6), cognitive impairment (5/6), movement disorder (3/6) and seizures (2/6).

Only 2 individuals present gait ataxia and intention tremor (mild/minimal in one case), with only mild cerebellar atrophy identified in one patient on brain MRI.
Created: 12 Nov 2020, 5:07 p.m. | Last Modified: 12 Nov 2020, 5:09 p.m.
Panel Version: 2.24

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Leukodystrophy, hypomyelinating, 16 OMIM:617964

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Cerebellar signs including ataxia prominent.
Sources: Expert list
Created: 13 Sep 2020, 7:26 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Leukodystrophy, hypomyelinating, 16, MIM# 617964

Publications

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • Leukodystrophy, hypomyelinating, 16, OMIM:617964
  • Leukodystrophy, hypomyelinating, 16, MONDO:0054791
Tags
missense
OMIM
613413
Clinvar variants
Variants in TMEM106B
Penetrance
None
Publications
Mode of Pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panels with this gene

History Filter Activity

12 Nov 2020, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: TMEM106B were changed from Leukodystrophy, hypomyelinating, 16, MIM# 617964 to Leukodystrophy, hypomyelinating, 16, OMIM:617964; Leukodystrophy, hypomyelinating, 16, MONDO:0054791

12 Nov 2020, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag missense tag was added to gene: TMEM106B.

12 Nov 2020, Gel status: 2

Set mode of pathogenicity

Arina Puzriakova (Genomics England Curator)

Mode of pathogenicity for gene: TMEM106B was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

12 Nov 2020, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: TMEM106B were set to 29186371; 29444210

12 Nov 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: tmem106b has been classified as Amber List (Moderate Evidence).

13 Sep 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: TMEM106B was added gene: TMEM106B was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list Mode of inheritance for gene: TMEM106B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TMEM106B were set to 29186371; 29444210 Phenotypes for gene: TMEM106B were set to Leukodystrophy, hypomyelinating, 16, MIM# 617964 Review for gene: TMEM106B was set to GREEN gene: TMEM106B was marked as current diagnostic