DDG2P
Gene: DMPK

DMPK (DM1 protein kinase)
EnsemblGeneIds (GRCh38): ENSG00000104936
EnsemblGeneIds (GRCh37): ENSG00000104936
OMIM: 605377, Gene2Phenotype
DMPK is in 17 panels

5 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: This gene has now been demoted from Green to Red despite having a gene-disease association with 'definitive' rating in the DD panel in G2P. This is because the disease-causing mechanism is an amplified trinucleotide CTG repeat in the 3'UTR (currently NGS unreportable), rather than SNVs within the gene.
Created: 9 Oct 2023, 5:57 p.m. | Last Modified: 9 Oct 2023, 5:57 p.m.

Panel Version: 3.72

The DDG2P confidence category for the disease DYSTROPHIA MYOTONICA TYPE 1, OMIM:160900 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure.
Created: 4 Oct 2023, 5:08 p.m. | Last Modified: 4 Oct 2023, 5:08 p.m.

Panel Version: 3.12

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

Phenotypes
DYSTROPHIA MYOTONICA TYPE 1, OMIM:160900

Mode of pathogenicity
Other

Created: 4 Oct 2023, 5:08 p.m.
Last Modified: 4 Oct 2023, 5:08 p.m.
Panel version: 3.12

Eleanor Williams (Genomics England Curator)

Leaving the GMS tags on this gene as a reminder that this gene should be demoted to red after the next update to make the panel be in line with the latest Developmental Disorders panel in Gene2Phenotype. Although the gene may have a strong rated gene-disease association in Gene2Phenotype for PanelApp and the Genomics England pipeline it should be the STR that is rated green.

Leaving it green for now is not considered high clinical risk.
Created: 27 Jul 2022, 1:56 p.m. | Last Modified: 27 Jul 2022, 1:56 p.m.

Panel Version: 2.76

Created: 27 Jul 2022, 1:56 p.m.
Last Modified: 27 Jul 2022, 1:56 p.m.
Panel version: 2.76

Arina Puzriakova (Genomics England Curator)

Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism. MOI should be changed to 'Other' to maintain consistency with other panels
Created: 9 Nov 2021, 3:31 p.m. | Last Modified: 9 Nov 2021, 3:31 p.m.

Panel Version: 2.53

Comment on list classification: This gene should be demoted from Green to Red at the next GMS review due to the disease-causing mechanism - genetic defect is an amplified trinucleotide CTG repeat in the 3'UTR (currently NGS unreportable), rather than SNVs within the gene.

However, the evidence level for this expansion is high (it is a confirmed DD gene for DYSTROPHIA MYOTONICA TYPE 1), and as DDG2P is a component of the Paediatric disorders super panel, the DMPK_CTG STR will be added to the panel to capture this entity and ensure that cases are detected.
Created: 9 Jul 2021, 12:35 p.m. | Last Modified: 9 Jul 2021, 12:35 p.m.

Panel Version: 2.35

Created: 9 Jul 2021, 12:35 p.m.
Last Modified: 9 Jul 2021, 12:35 p.m.
Panel version: 2.35

Dmitrijs Rots (Children's Clinical University Hospital)

Red List (low evidence)

Causes myotinic dystrophy only due to STR expansion, not SNVs.
Created: 30 Jun 2021, 11:05 a.m. | Last Modified: 30 Jun 2021, 11:06 a.m.

Panel Version: 2.29

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Created: 30 Jun 2021, 11:05 a.m.
Last Modified: 30 Jun 2021, 11:06 a.m.
Panel version: 2.29

Rebecca Foulger (Genomics England curator)

I don't know

Original DDG2P rating: confirmed. DDG2P mode of pathogenicity: dominant negative
Created: 19 Nov 2018, 11:29 a.m.

Created: 19 Nov 2018, 11:29 a.m.

Panel version: 0.2

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Expert Review Red
DD-Gene2Phenotype

Phenotypes

DYSTROPHIA MYOTONICA TYPE 1, OMIM:160900

Tags

nucleotide-repeat-expansion currently-ngs-unreportable

OMIM

605377

Clinvar variants

Variants in DMPK

Penetrance

None

Mode of Pathogenicity

Other

Panels with this gene