ClinVar Miner

Submissions for variant NM_001244008.2(KIF1A):c.798+1G>A

dbSNP: rs1064796565
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484840 SCV000573389 likely pathogenic not provided 2017-02-23 criteria provided, single submitter clinical testing The c.798+1G>A variant in the KIF1A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 7. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.798+1G>A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.798+1G>A as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001851257 SCV002303920 pathogenic Hereditary spastic paraplegia 30; Neuropathy, hereditary sensory, type 2C; Intellectual disability, autosomal dominant 9 2025-01-15 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 7 of the KIF1A 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 KIF1A are known to be pathogenic (PMID: 21820098). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with autosomal dominant KIF1A-associated neurological disorder (PMID: 33880452). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 423668). 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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