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Intellectual disability

Gene: ABCC9

Green List (high evidence)

ABCC9 (ATP binding cassette subfamily C member 9)
EnsemblGeneIds (GRCh38): ENSG00000069431
EnsemblGeneIds (GRCh37): ENSG00000069431
OMIM: 601439, Gene2Phenotype
ABCC9 is in 15 panels

7 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Intellectual impairment has been reported in individuals with loss-of-function variants and a percentage of those with gain-of-function variants. ID is typically mild, however it is plausible that patients may still be tested for this panel, particularly if recruited under Coffin-Siris-like coarse facial features which can be associated with this gene. Therefore, maintaining Green gene rating.

Comment on mode of inheritance: Leaving MOI as Monoallelic as only 2 families with the same biallelic variant (possible founder variant) reported to date (PMID:31575858), and patients with biallelic variants would still be picked up by the Genomics England pipeline.
Created: 22 Jan 2021, 10:41 a.m. | Last Modified: 26 Jan 2021, 11:48 a.m.
Panel Version: 3.740
Copied from review by Tracy Lester (Genetics laboratory, Oxford UK) on the DDG2P panel, 14 Jul 2020:

"Authors report 6 cases from 2 families, all with homozygous c.1320+1G>A. Phenotype of mild ID, similar facies, myopathy, cerebral white matter hyperintensities, and cardiac systolic dysfunction in the oldest cases.
'This mutation results in an in-frame deletion of exon 8, which results in non-functional KATP channels in recombinant assays. SUR2 loss-of-function causes fatigability and cardiac dysfunction in mice, and reduced activity, cardiac dysfunction and ventricular enlargement in zebrafish. We term this channelopathy resulting from loss-of-function of SUR2-containing KATP channels ABCC9-related Intellectual disability Myopathy Syndrome (AIMS). The phenotype differs from Cantú syndrome, which is caused by gain-of-function ABCC9 mutations, reflecting the opposing consequences of KATP loss- versus gain-of-function'.
Just 2 families so doesn't fulfil criteria for green gene yet in terms of ID - amber"
Created: 22 Jan 2021, 10:16 a.m. | Last Modified: 22 Jan 2021, 10:16 a.m.
Panel Version: 3.717

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
mild ID; similar facies, myopathy; cerebral white matter hyperintensities; cardiac systolic dysfunction

Publications

Caroline Wright (Sanger)

Red List (low evidence)

Phenotypes
CANTU SYNDROME HYPERTRICHOTIC OSTEOCHONDRODYSPLASIA

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_gilissen_2014_known;in_UKGTN_v12 . Main mutation mechanism : Activating
Created: 27 Jul 2017, 4:57 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; gilissen_2014_known; UKGTN_v12; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; GEL_ID_red_20160217; neuro_20160418_strict; Activating. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 11:54 a.m.

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

Publications

Mode of pathogenicity
Other

Ellen McDonagh (Genomics England Curator)

This was promoted from red to green due to application to patients recruited under coarse facial features including Coffin-Siris-like disorders.
Created: 28 Nov 2016, 1:51 p.m.

Alice Gardham (Genomics England)

Comment on list classification: A minority of affected individuals will have some intellectual disability. Mild motor delay common due to hypotonia
Created: 28 Nov 2016, 1:42 p.m.
Comment on list classification: A minority of affected individuals will have some intellectual disability. Mild motor delay common due to hypotonia
Created: 28 Nov 2016, 1:42 p.m.

Lu Raymond (university of cambridge )

Red List (low evidence)

Alice Gardham (North West Thames Genetics)

Green List (high evidence)

Phenotypes
Cantu

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Victorian Clinical Genetics Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Cardiomyopathy, dilated, 10, 608569
  • Atrial fibrillation, familial, 12, 614050
  • Hypertrichotic osteochondrodysplasia, 239850
  • CANTU SYNDROME HYPERTRICHOTIC OSTEOCHONDRODYSPLASIA
OMIM
601439
Clinvar variants
Variants in ABCC9
Penetrance
Complete
Panels with this gene

History Filter Activity

26 Jan 2021, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review was removed from gene: ABCC9.

22 Jan 2021, Gel status: 3

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: abcc9 has been classified as Green List (High Evidence).

22 Jan 2021, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: ABCC9.

28 Sep 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to ABCC9.

12 Mar 2018, Gel status: 3

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

12 Jan 2018, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for ABCC9 were set to Cardiomyopathy, dilated, 10, 608569; Atrial fibrillation, familial, 12, 614050; Hypertrichotic osteochondrodysplasia, 239850; CANTU SYNDROME HYPERTRICHOTIC OSTEOCHONDRODYSPLASIA

28 Nov 2016, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for ABCC9 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

28 Nov 2016, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for ABCC9 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

28 Nov 2016, Gel status: 4

Gene classified by Genomics England curator

Alice Gardham (Genomics England)

This gene has been classified as Green List (High Evidence).

28 Nov 2016, Gel status: 4

Gene classified by Genomics England curator

Alice Gardham (Genomics England)

This gene has been classified as Green List (High Evidence).

28 Nov 2016, Gel status: 4

Gene classified by Genomics England curator

Alice Gardham (Genomics England)

This gene has been classified as Green List (High Evidence).

13 Nov 2015, Gel status: 1

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

ABCC9 was added to Intellectual disabilitypanel. Source: Expert Review Red

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

ABCC9 was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen