Congenital myaesthenic syndrome

Gene: SYT2

Green List (high evidence)

SYT2 (synaptotagmin 2)
EnsemblGeneIds (GRCh38): ENSG00000143858
EnsemblGeneIds (GRCh37): ENSG00000143858
OMIM: 600104, Gene2Phenotype
SYT2 is in 7 panels

5 reviews

Zornitza Stark (Australian Genomics)

Green List (high evidence)

New MOI:

Mono-allelic disease, PMID 25192047 and 30533528: dominant missense variants in SYT2 reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment in three families. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated.

Bi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function.
Created: 2 Nov 2020, 9:52 a.m. | Last Modified: 2 Nov 2020, 9:52 a.m.
Panel Version: 2.5

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040

Publications

Ivone Leong (Genomics England Curator)

Comment on list classification: Promoted from red to green. PMID: 30533528 reported on a third unrelated case with a new variant in this gene. Therefore there is enough evidence to support a gene-disease association.
Created: 7 Aug 2019, 2:24 p.m. | Last Modified: 7 Aug 2019, 2:24 p.m.
Panel Version: 1.52

Louise Daugherty (Genomics England Curator)

I don't know

Review and rating from Michael Oldridge (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust), submitted by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.
Created: 30 Apr 2019, 9:30 a.m.

Michael Oldridge (NHS)

Green List (high evidence)

Herrmann et al describe 2 multigenerational families with AD inheritiance with a combined LOD score of approx 2.4. Nerve conductions studies fit with a presynaptic CMS in both families (26519543 Whittaker 2015. also shown by Herrmann). Herrmann also constructed a drosophila model of one of the human mutations demonstrating dominant negative effect in synaptic transmission. 2 unrelated families, plus functional model - Green
Created: 29 Apr 2019, 4:33 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Myasthenic syndrome, congenital, 7, presynaptic, 616040

Publications

Rebecca Foulger (Genomics England curator)

Comment on list classification: Kept rating as Red: only reported in 2 families so far.
Created: 2 Feb 2017, 3:54 p.m.
PMID:25192047, Hermann et al 2014, establishes another presynaptic myasthenic syndrome: In 4 affected members of a 3-generation American family. they identified a heterozygous c.920A-C, D307A mutation in SYT2. In 6 affected members of a 3-generation family from the UK, they identified a heterozygous c.923C-T, P308L mutation in SYT2.
Created: 2 Feb 2017, 3:43 p.m.
Comment on mode of inheritance: Mode of inheritance confirmed by OMIM.
Created: 2 Feb 2017, 3:39 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • NHS GMS
  • Wessex and West Midlands GLH
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Myasthenic syndrome, congenital, 7, presynaptic, OMIM:616040
OMIM
600104
Clinvar variants
Variants in SYT2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

22 Mar 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: SYT2 were changed from Myasthenic syndrome, congenital, 7, presynaptic, 616040 to Myasthenic syndrome, congenital, 7, presynaptic, OMIM:616040

22 Mar 2021, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: SYT2 were set to 26519543; 25192047; 27472506 (Review); 30533528

7 Aug 2019, Gel status: 3

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: syt2 has been classified as Green List (High Evidence).

7 Aug 2019, Gel status: 1

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: SYT2 were set to 26519543; 25192047; 27472506 (Review)

30 Apr 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: SYT2 were set to 26519543

29 Apr 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene SYT2 were changed from 25192047; 27472506 (Review); 26519543 to 26519543

29 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to SYT2.

29 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source Wessex and West Midlands GLH was added to SYT2.

22 Feb 2017, Gel status: 1

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

22 February 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.

2 Feb 2017, Gel status: 1

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Red List (Low Evidence).

2 Feb 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for SYT2 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

2 Feb 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for SYT2 were set to Myasthenic syndrome, congenital, 7, presynaptic, 616040

28 Apr 2015, Gel status: 1

Added New Source

GEL ()

SYT2 was added to Congenital myaestheniapanel. Sources: Radboud University Medical Center, Nijmegen