ClinVar Miner

Submissions for variant NM_014946.3(SPAST):c.1617-1G>A (rs1553319526)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000696816 SCV000825395 pathogenic Spastic paraplegia 4, autosomal dominant 2018-04-06 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 14 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 individuals affected with hereditary spastic paraplegia (PMID: 22960362, Invitae). A different variant affecting this nucleotide (c.1617-1G>T) has been determined to be pathogenic (PMID: 12161613). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be 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). For these reasons, this variant has been classified as Pathogenic.

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