ClinVar Miner

Submissions for variant NM_014946.3(SPAST):c.1245+1G>A (rs875989878)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000211536 SCV000268514 pathogenic Spastic paraplegia 4, autosomal dominant 2016-02-19 criteria provided, single submitter clinical testing This inherited mutation in the SPAST gene is the likely cause of the familial spastic paraplegia observed in the patient and in her father.
Invitae RCV000211536 SCV000645344 pathogenic Spastic paraplegia 4, autosomal dominant 2018-08-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 9 of the SPAST gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with hereditary spastic paraplegia and has been reported to segregate with hereditary spastic paraplegia in a single family (PMID: 11309678, 26600529, 22552817, 22960362). This variant is also known as IVS9+1G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 226113) Experimental studies have shown that this variant results in exon 9 skipping (PMID: 11309678). 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). For these reasons, this variant has been classified as Pathogenic.

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