Clinical Domain Working Groups

The goal of this VCEP is to curate clinically relevant variants in the ABCA4 gene, which is a 50 exon gene that has been associated with multiple phenotypes that deserves the full attention of a single VCEP. The ABCA4 gene spans 128kb and encodes a 2273 amino acid protein that removes N-retinylidene-PE, a waste product made during phototransduction, from photoreceptor cells in the retina. This gene has been associated with several inherited retinal dystrophies, such as Stargardt disease, retinitis pigmentosa, cone-rod dystrophy and other inherited maculopathies. Typically, diseases associated with ABCA4 variants are associated with recessive modes. At this time, the VCEP plans to focus its curation on autosomal recessive maculopathies as a result of biallelic pathogenic ABCA4 variants. The ClinGen Retina GCEP has reviewed the ABCA4 gene and decided to lump all recessive forms of retinopathies into one group of ABCA4-related retinopathies, which reached a definitive gene/disease classification.