Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute for Medical Genetics and Human Genetics, |
RCV001250476 | SCV001364077 | uncertain significance | Primary dilated cardiomyopathy; Cerebellar ataxia; Intellectual disability; Polyneuropathy; Spastic paraparesis | criteria provided, single submitter | clinical testing | In this patient, two sequence variants were detected in the GBA2 gene, each in a heterozygous state. The GBA2 gene codes for the non-lysosomal enzyme ß-glucosidase 2. Bi-allelic mutations in the GBA2 gene cause the clinical picture of autosomal recessive spastic paraplegia type 46 (MIM # 614409). So far, about 20 mutations in the GBA2 gene have been described as causative, 11 of which are missense mutations (HMGD Professional 2019.1). It is a neurodegenerative disease characterized by slowly progressing spastic paraplegia and cerebellar disorders (cerebellar ataxia, dysarthria). Some patients have also developed cognitive impairment, axonal polyneuropathy and cataracts (Martin et al, 2013; Hammer et al, 2013). The sequence variant c.1444A>C leads to the exchange of the highly conserved amino acid asparagine to histidine at position 482. Several prediction programs classify this exchange as pathogenic. The variant has not yet been described in ExAC or gnomAD. In summary, there are two variants (PM2) that have not been described so far. After consultation with clinicians, they fit the clinical picture (PP4) and are classified as pathogenic by several prediction programs (PP3). According to the ACMG criteria, the variants must currently be formally classified as variants of unclear significance (class III). |