ClinVar

Description

The maternally inherited T703M pathogenic variant in the BICD2 gene has been reported previously as aheterozygous pathogenic variant in a father and son with spinal muscular atrophy (Neveling et al., 2013). Usingimmunoblot analysis, fibroblasts from the affected patients had reduced BICD2 levels compared to control fibroblastsand using immunostaining, the fibroblasts from the affected patients showed strong Golgi fragmentation and BICD2trapped in the Golgi (Neveling et al., 2013). The T703M variant was not observed with any significant frequency inapproximately 6500 individuals of European and African American ancestry in the NHLBI Exome SequencingProject, indicating it is not a common benign variant in these populations. The T703M variant is a non-conservativeamino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity,charge, size and/or other properties. This substitution occurs in the 3rd coiled-coil domain at a position that isconserved across species. In silico analysis predicts this variant is probably damaging to the proteinstructure/function. We interpret T703M as a pathogenic variant.