ClinVar Miner

Submissions for variant NM_014946.4(SPAST):c.1493+1G>A

dbSNP: rs1553318351
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001219396 SCV001391332 pathogenic Hereditary spastic paraplegia 4 2024-09-27 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 12 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 SPAST-related conditions (PMID: 20491894). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 948187). 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.
Athena Diagnostics 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.

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