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Intellectual disability

Gene: ABCA2

Amber List (moderate evidence)

ABCA2 (ATP binding cassette subfamily A member 2)
EnsemblGeneIds (GRCh38): ENSG00000107331
EnsemblGeneIds (GRCh37): ENSG00000107331
OMIM: 600047, Gene2Phenotype
ABCA2 is in 3 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Although not all published cases have a diagnosis of ID (and of those that do, only 1 family with moderate ID), global developmental delay is the most commonly observed features and therefore, this panel may be the most applicable for detecting patients.

Rating Amber, but this will be flagged for review at the next GMS panel update to assess the relevance of the phenotype and determine whether there is sufficient evidence to rate this gene Green (added 'for-review' tag).
Created: 16 Nov 2020, 11:25 a.m. | Last Modified: 16 Nov 2020, 11:25 a.m.
Panel Version: 3.533
Associated with relevant phenotype in OMIM, but currently not in Gene2Phenotype.

At least 7 individuals from 4 unrelated families reported at present with different biallelic variants in the ABCA2 gene. Overlapping clinical features include psychomotor delay (6/7), microcephaly (3/7), ataxia (3/7), and epilepsy (2/7). 4 cases in 3 families had a formal diagnosis of ID (2 moderate, 1 mild, 1 unknown severity).
Created: 16 Nov 2020, 11:11 a.m. | Last Modified: 16 Nov 2020, 11:11 a.m.
Panel Version: 3.532

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual developmental disorder with poor growth and with or without seizures or ataxia, OMIM: 618808

Publications

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808).

There are 3 relevant publications (01-07-2020) :
- Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations.
- Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures.
- Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype.

All subjects harbored biallelic pLoF variants.

N.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency.

Overall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals).
Sources: Literature
Created: 13 Jul 2020, 6:24 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Intellectual developmental disorder with poor growth and with or without seizures or ataxia, OMIM:618808
  • Intellectual developmental disorder with poor growth and with or without seizures or ataxia, MONDO:0032930
Tags
for-review
OMIM
600047
Clinvar variants
Variants in ABCA2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

16 Nov 2020, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: ABCA2 were changed from Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808 to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, OMIM:618808; Intellectual developmental disorder with poor growth and with or without seizures or ataxia, MONDO:0032930

16 Nov 2020, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: ABCA2.

16 Nov 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: abca2 has been classified as Amber List (Moderate Evidence).

13 Jul 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: ABCA2 was added gene: ABCA2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799 Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808 Penetrance for gene: ABCA2 were set to Complete Review for gene: ABCA2 was set to GREEN