Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002625104 | SCV003519092 | pathogenic | Hereditary spastic paraplegia 4 | 2024-10-03 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 12 of the SPAST gene. It does not directly change the encoded amino acid sequence of the SPAST protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with clinical features of hereditary spastic paraplegia (internal data). Invitae Evidence Modeling of clinical and family history, age, sex, and reported ancestry of multiple individuals with this SPAST variant has been performed. This variant is expected to be pathogenic with a positive predictive value of at least 99%. This is a validated machine learning model that incorporates the clinical features of 3,690 individuals referred to our laboratory for SPAST testing. ClinVar contains an entry for this variant (Variation ID: 2199724). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |