Intellectual disability
Gene: ABCA2

ABCA2 (ATP binding cassette subfamily A member 2)
EnsemblGeneIds (GRCh38): ENSG00000107331
EnsemblGeneIds (GRCh37): ENSG00000107331
OMIM: 600047, Gene2Phenotype
ABCA2 is in 4 panels

3 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.

Panel Version: 3.1510

Created: 9 Mar 2022, 3:40 p.m.
Last Modified: 9 Mar 2022, 3:40 p.m.
Panel version: 3.1510

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

Created: 16 Nov 2020, 11:11 a.m.
Last Modified: 16 Nov 2020, 11:11 a.m.
Panel version: 3.532

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

Created: 13 Jul 2020, 6:24 p.m.

Panel version: 3.170

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green

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

OMIM

600047

Clinvar variants

Variants in ABCA2

Penetrance

Complete

Publications

Panels with this gene