Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003525270 | SCV004292431 | pathogenic | Hereditary spastic paraplegia 4 | 2023-07-29 | criteria provided, single submitter | clinical testing | This variant is also known as 1662-2A>T. This sequence change affects an acceptor splice site in intron 13 of the SPAST gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SPAST are known to be pathogenic (PMID: 20932283). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with hereditary spastic paraplegia (PMID: 10699187; Invitae). 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. |