Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001218499 | SCV001390382 | pathogenic | Hereditary spastic paraplegia 4 | 2019-04-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SPAST are known to be pathogenic (PMID: 20932283). Disruption of this splice site has been observed in several individuals and families affected with hereditary spastic paraplegia (PMID: 10699187, 16832076, 20718791). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 7 of the SPAST gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |