Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001883381 | SCV002143780 | likely pathogenic | Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures | 2023-03-10 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Ile189 amino acid residue in BICD2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25497877, 28883039). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 189 of the BICD2 protein (p.Ile189Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of BICD2-related conditions (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1375587). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt BICD2 function. |