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Intellectual disability
Gene: ABCC9

ABCC9 (ATP binding cassette subfamily C member 9)
EnsemblGeneIds (GRCh38): ENSG00000069431
EnsemblGeneIds (GRCh37): ENSG00000069431
OMIM: 601439, Gene2Phenotype
ABCC9 is in 14 panels

10 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Created: 26 Sep 2024, 2:57 p.m. | Last Modified: 26 Sep 2024, 2:57 p.m.

Panel Version: 7.41

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Created: 26 Sep 2024, 2:57 p.m.
Last Modified: 26 Sep 2024, 2:57 p.m.
Panel version: 7.41

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Comment on mode of pathogenicity: Loss of function variants do cause the phenotype of Intellectual disability and myopathy syndrome (OMIM:619719) , which is relevant to this panel.
Created: 6 Feb 2024, 4:12 p.m. | Last Modified: 6 Feb 2024, 4:12 p.m.

Panel Version: 5.448

Seven homozygous loss of function ABCC9 variants have been reported in seven unrelated cases of Intellectual disability and myopathy syndrome (OMIM:619719)(PMID: 31575858; 38217872). In vivo studies of abcc9 LoF in zebrafish, revealed an exacerbated motor response to pentylenetetrazole, a pro-convulsive drug, consistent with impaired neurodevelopment associated with an increased seizure susceptibility.(PMID: 38217872). Heterozygous parents of the cases, did not show a consistent phenotype, although intrauterine death was reported in two families (PMID: 38217872). In family 4 the fetus was homozygous for c.1858C>T, p.(Arg620Ter) and in family 8 the parents were both heterozygous for c.2140_2141del, p.(Leu714SerfsTer7), but analysis of the fetus was not possible.
Created: 6 Feb 2024, 3:34 p.m. | Last Modified: 6 Feb 2024, 3:44 p.m.

Panel Version: 5.445

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability and myopathy syndrome, OMIM:619719; intellectual disability and myopathy syndrome, MONDO:0859224

Publications

38217872

Created: 6 Feb 2024, 3:34 p.m.
Last Modified: 6 Feb 2024, 3:44 p.m.
Panel version: 5.445

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

This gene is currently green for monoallelic inheritance but the associated review relates to cases with biallelic inheritance. The MOI for this gene should be amended to biallelic only. Monoallelic variants are associated with Cantu syndrome which is not primarily an ID disorder or DCM.
Created: 6 Feb 2024, 4:57 p.m. | Last Modified: 6 Feb 2024, 4:57 p.m.

Panel Version: 5.449

This gene is currently green on the ID panel for monoallelic inheritance. Monoallelic variants in this gene are associated with Cantu syndrome, which is primarily characterised by hypertrichosis, facial dysmorphism and heart defects. According to genereviews ' Developmental delays are common, but intellect is typically normal; behavioral problems can include attention-deficit/hyperactivity disorder, autism spectrum disorder, obsessive-compulsive disorder, anxiety, and depression.' Therefore this gene probably should not be green for this disorder on the ID panel. There is some evidence for biallelic variants being associated with ID but insufficient data currently for this to be elevated to green for biallelic inheritance - suggest downgrading to amber for biallelic inheritance only
Created: 25 Jan 2024, 10:07 a.m. | Last Modified: 25 Jan 2024, 10:07 a.m.

Panel Version: 5.409

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Created: 25 Jan 2024, 10:07 a.m.
Last Modified: 25 Jan 2024, 10:07 a.m.
Panel version: 5.449

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

31575858

Created: 22 Jan 2021, 10:16 a.m.
Last Modified: 26 Jan 2021, 11:48 a.m.
Panel version: 3.717

Caroline Wright (Sanger)

Red List (low evidence)

Phenotypes
CANTU SYNDROME HYPERTRICHOTIC OSTEOCHONDRODYSPLASIA

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

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

25529582
24896178
Version 12 ukgtn.nhs.uk

Mode of pathogenicity
Other

Created: 2 Aug 2017, 1:40 p.m.

Panel version: 1.354

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.

Created: 28 Nov 2016, 1:51 p.m.

Panel version: 1.12

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.

Created: 28 Nov 2016, 1:42 p.m.

Panel version: 1.12

Lu Raymond (university of cambridge )

Red List (low evidence)

Created: 23 Feb 2016, 11:25 a.m.

Panel version: 0.306

Alice Gardham (North West Thames Genetics)

Green List (high evidence)

Phenotypes
Cantu

Created: 29 Jan 2016, 9:32 p.m.

Panel version: Imported from "Coarse facial features including Coffin-Siris-like disorders" panel version 0.7

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

NHS GMS
Expert Review Green
Victorian Clinical Genetics Services
Radboud University Medical Center, Nijmegen

Phenotypes

Intellectual disability and myopathy syndrome, OMIM:619719
intellectual disability and myopathy syndrome, MONDO:0859224

OMIM

601439

Clinvar variants

Variants in ABCC9

Penetrance

Complete

Publications

Panels with this gene

History Filter Activity

26 Sep 2024, Gel status: 3

Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q1_24_MOI was removed from gene: ABCC9. Tag Q1_24_NHS_review was removed from gene: ABCC9.

26 Sep 2024, Gel status: 3

Added New Source, Set mode of inheritance

Achchuthan Shanmugasundram (Genomics England Curator)

Source NHS GMS was added to ABCC9. Mode of inheritance for gene ABCC9 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal

6 Feb 2024, Gel status: 3