Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000705026 | SCV000834005 | pathogenic | Familial aplasia of the vermis | 2023-05-04 | criteria provided, single submitter | clinical testing | This sequence change results in a frameshift in the INPP5E gene (p.Cys641Serfs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 4 amino acid(s) of the INPP5E protein and extend the protein by 3 additional amino acid residues. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the INPP5E protein in which other variant(s) (p.Cys641Arg) have been determined to be pathogenic (PMID: 23386033). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 581255). This variant has not been reported in the literature in individuals affected with INPP5E-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). |