Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001219396 | SCV001391332 | pathogenic | Hereditary spastic paraplegia 4 | 2019-07-26 | 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). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 20491894). This variant has been observed to segregate with hereditary spastic paraplegia in a family (PMID: 20491894). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 12 of the SPAST gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Athena Diagnostics Inc | RCV001664760 | SCV001880487 | pathogenic | not provided | 2021-03-23 | criteria provided, single submitter | clinical testing | This variant is expected to severely impact normal RNA splicing, and consequently, protein structure and/or function. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. |