ClinVar Miner

Submissions for variant NM_025137.4(SPG11):c.869+1G>A

dbSNP: rs312262721
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000034268 SCV000825310 pathogenic Hereditary spastic paraplegia 11 2023-02-11 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the SPG11 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 SPG11 are known to be pathogenic (PMID: 19105190, 20110243, 22154821, 26556829). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with autosomal recessive hereditary spastic paraplegia (PMID: 18079167). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 41367). 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.
3billion RCV000034268 SCV002521670 pathogenic Hereditary spastic paraplegia 11 2022-05-22 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV000041367). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Genome-Nilou Lab RCV000034268 SCV002764198 pathogenic Hereditary spastic paraplegia 11 criteria provided, single submitter clinical testing
GeneReviews RCV000034268 SCV000058208 not provided Hereditary spastic paraplegia 11 no assertion provided literature only

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