Genes in panel

Neurodegenerative disorders - adult onset

Gene: SNCB

Amber List (moderate evidence)

SNCB (synuclein beta)
EnsemblGeneIds (GRCh38): ENSG00000074317
EnsemblGeneIds (GRCh37): ENSG00000074317
OMIM: 602569, Gene2Phenotype
SNCB is in 2 panels

3 reviews

Eleanor Williams (Genomics England Curator)

I don't know

2 cases reported by Ohtake et al 2004. One sporadic and one familial but with reduced penetrance. Targeted sequencing of only 2 candidate genes. Functional studies of Psol et al 2021 suggest that the two variants identified cause neuropathological lesions.

PMID: 33760043 - Psol et al 2021 - expressed the V70M and P123H variants found by Ohtake et al 2004 using adeno-associated viral vectors in dopaminergic and non-dopaminergic neurons in vitro and in vivo. They found that both mutations cause distinct and mutually exclusive neuropathological lesions.

PMID: 15365127 - Ohtake et al 2004 - looked at 33 sporadic cases of dementia with Lewy bodies (DLB) and 10 kindreds segregating DLB and screened the alpha-synuclein and beta-synuclein genes for variants. 2 unrelated patients were found to have variants in the beta-synuclein gene (SNCB) - G208A:V70M (sporadic case) and C368A:P123H (familial case). 3 of the proband's cousins, all over age 70, in the familial case were screened for the P123H variant. 1 cousin who was heterozygous and 1 homozygous had possible signs of DLB. 1 heterozygous cousin age 80 had no signs of DLB. Authors suggest this is an autosomal dominant trait with reduced penetrance . The clinical description of the familial case was first described in PMID: 12641375 (Bonner et al 2003).
Created: 5 May 2021, 5:30 p.m. | Last Modified: 5 May 2021, 5:30 p.m.
Panel Version: 2.174

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

Phenotypes
Dementia, Lewy body, OMIM:127750

Publications

Louise Daugherty (Genomics England Curator)

I don't know

As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Created: 20 Sep 2019, 4:19 p.m. | Last Modified: 20 Sep 2019, 4:19 p.m.
Panel Version: 1.106
Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.
Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.
Panel Version: 1.74

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

I don't know

One report of two variants. Mouse model appears to support pathogenicity.
Created: 23 Jul 2019, 3:35 p.m. | Last Modified: 23 Jul 2019, 3:35 p.m.
Panel Version: 1.72

Mode of inheritance
Unknown

Phenotypes
Dementia, Lewy body, 127750

Publications

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

Details

Mode of Inheritance
Unknown
Sources
  • Expert Review Amber
  • NHS GMS
  • Yorkshire and North East GLH
Phenotypes
  • Dementia, Lewy body, OMIM:127750
OMIM
602569
Clinvar variants
Variants in SNCB
Penetrance
None
Publications
Panels with this gene

History Filter Activity

29 Mar 2021, Gel status: 2

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: SNCB were changed from Dementia, Lewy body, 127750 to Dementia, Lewy body, OMIM:127750

20 Sep 2019, Gel status: 2

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Amber was added to SNCB. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)

23 Jul 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene SNCB were changed from to 15365127; 21045828

23 Jul 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to SNCB.

23 Jul 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to SNCB.

25 Jan 2019, Gel status: 1

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

Rebecca Foulger: Gene awaiting curator evaluati

18 Dec 2018, Gel status: 1

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

Rebecca Foulger (Genomics England curator)

gene: SNCB was added gene: SNCB was added to Neurodegenerative disorders - adult onset. Sources: Expert Review Red Mode of inheritance for gene: SNCB was set to Unknown Phenotypes for gene: SNCB were set to Dementia, Lewy body, 127750