ClinVar Miner

Submissions for variant NM_014946.4(SPAST):c.1617-2A>G

dbSNP: rs1553319524
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000993067 SCV001145776 pathogenic not provided 2018-10-01 criteria provided, single submitter clinical testing The variant disrupts a canonical splice site, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and not found in general population data.
Labcorp Genetics (formerly Invitae), Labcorp RCV001223606 SCV001395762 pathogenic Hereditary spastic paraplegia 4 2024-07-15 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. 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 hereditary spastic paraplegia (PMID: 12161613, 16682546, 22960362). ClinVar contains an entry for this variant (Variation ID: 805512). 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.

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