White matter disorders and cerebral calcification - narrow panel

Gene: TMEM106B

The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.

Created: 9 Mar 2022, 4:29 p.m. | Last Modified: 9 Mar 2022, 4:29 p.m.

Panel Version: 1.223

Green List (high evidence)

Comment on list classification: There are sufficient unrelated cases (6) to promote the rating to Green at the next GMS panel update - hypomyelinating leukodystrophy is the predominant feature of the disease presentation.

Created: 12 Nov 2020, 4:47 p.m. | Last Modified: 12 Nov 2020, 4:47 p.m.

Panel Version: 1.21

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).

Created: 12 Nov 2020, 3:16 p.m. | Last Modified: 12 Nov 2020, 3:16 p.m.

Panel Version: 1.20

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

Phenotypes
Leukodystrophy, hypomyelinating, 16 OMIM:617964

Publications

• 29186371
• 29444210
• 30643851
• 32595021

Green List (high evidence)

Five unrelated individuals reported with the same recurrent de novo missense variant in this gene, p.Asp252Asn. GoF mechanism postulated.

Created: 16 Sep 2020, 5:11 a.m. | Last Modified: 16 Sep 2020, 5:11 a.m.

Panel Version: 1.14

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Leukodystrophy, hypomyelinating, 16 617964

Publications

• 29186371
• 29444210
• 28728022
• 30643851

Mode of pathogenicity
Other