1. Panels
  2. Newborns additional phenotypes panel 2
  3. ABCC8
STRs in panel
Prev Next
Regions in panel
Prev Next

Newborns additional phenotypes panel 2

Gene: ABCC8

Amber List (moderate evidence)
ABCC8 (ATP binding cassette subfamily C member 8)
EnsemblGeneIds (GRCh38): ENSG00000006071
EnsemblGeneIds (GRCh37): ENSG00000006071
OMIM: 600509, Gene2Phenotype
ABCC8 is in 11 panels

2 reviews

Ivone Leong (Genomics England Curator)

Comment on list classification: Changed from Green to Amber. ABCC8 is associated with both Monoallelic and Biallelic forms of Diabetes mellitus, permanent neonatal 3, with or without neurologic features. However, the inclusion of monoallelic ABCC8 increases false positives and the pipeline cannot detect variants based on MOI for specific genes. So dominant MOI will not be included until additional pipeline rules are added.
Created: 20 Dec 2023, 3:57 p.m. | Last Modified: 20 Dec 2023, 3:57 p.m.
Panel Version: 0.21
Created: 20 Dec 2023, 3:57 p.m.
Last Modified: 20 Dec 2023, 3:57 p.m.
Panel version: 0.21

Mafalda Gomes (Genomics England Curator)

The mechanism of pathogenicity is gain-of-function (GOF).
Created: 5 Jul 2023, 3:11 p.m. | Last Modified: 5 Jul 2023, 3:11 p.m.
Panel Version: 0.9
ABCC8 curation results (clinicalgenome.org)
Created: 5 Jul 2023, 3:11 p.m. | Last Modified: 5 Jul 2023, 3:11 p.m.
Panel Version: 0.9
The mechanism for dominant cases is activating variants resulting in a KATP channel unable to close in response to ATP, impairing insulin secretion. The occasional recessive cases are caused by either (1) homozygosity or compound heterozygosity for partially activating variants or (2) a partially activating variant that only causes diabetes when inherited in trans with an inactivating variant. So, seems like LOF is rare and only causes disease when a GOF variant is in trans. But just to confirm, do we not want LOF prioritisation for AR? -> DB: I have taken your comment and added to spreadsheet to discuss with specialists
Created: 5 Jul 2023, 3:11 p.m. | Last Modified: 5 Jul 2023, 3:11 p.m.
Panel Version: 0.9
Created: 5 Jul 2023, 3:11 p.m.
Last Modified: 5 Jul 2023, 3:11 p.m.
Panel version: 0.9

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
Phenotypes
  • Diabetes mellitus, permanent neonatal 3, with or without neurologic features, autosomal dominant
OMIM
600509
Clinvar variants
Variants in ABCC8
Penetrance
None
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

6 Feb 2024, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: ABCC8 were changed from Diabetes mellitus, permanent neonatal 3, with or without neurologic features, autosomal recessive to Diabetes mellitus, permanent neonatal 3, with or without neurologic features, autosomal dominant

6 Feb 2024, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: ABCC8 were changed from Diabetes mellitus, permanent neonatal 3, with or without neurologic features to Diabetes mellitus, permanent neonatal 3, with or without neurologic features, autosomal recessive

20 Dec 2023, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: abcc8 has been classified as Amber List (Moderate Evidence).

14 Sep 2023, Gel status: 3

Set Phenotypes

Mafalda Gomes (Genomics England Curator)

Added phenotypes Diabetes mellitus, permanent neonatal 3, with or without neurologic features for gene: ABCC8

5 Jul 2023, Gel status: 3

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

Mafalda Gomes (Genomics England Curator)

gene: ABCC8 was added gene: ABCC8 was added to Newborns additional phenotypes panel 2. Sources: Expert Review Green Mode of inheritance for gene: ABCC8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: ABCC8 were set to Diabetes mellitus, permanent neonatal 3, with or without neurologic features Mode of pathogenicity for gene: ABCC8 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments