Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001046769 | SCV001210683 | likely pathogenic | Hereditary spastic paraplegia 11 | 2023-04-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.His2388Thrfs*6) in the SPG11 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 56 amino acid(s) of the SPG11 protein. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with clinical features of SPG11-related conditions (PMID: 33624863; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as p.Gln2387ThrfsTer7. ClinVar contains an entry for this variant (Variation ID: 844026). This variant disrupts the C-terminus of the SPG11 protein. Other variant(s) that disrupt this region (p.Glu2417Leufs*9) have been observed in individuals with SPG11-related conditions (Invitae). This suggests that this may be a clinically significant region of the protein. 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. |