Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000444722 | SCV000530486 | uncertain significance | not provided | 2016-08-08 | criteria provided, single submitter | clinical testing | The R160C variant in the BICD2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R160C variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R160C variant is a non-conservative amino 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 at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R160C as a variant of uncertain significance. |
Labcorp Genetics |
RCV001369357 | SCV001565793 | uncertain significance | Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures | 2024-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 160 of the BICD2 protein (p.Arg160Cys). This variant is present in population databases (rs754493702, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with BICD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 388229). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BICD2 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |