ClinVar Miner

Submissions for variant NM_015346.4(ZFYVE26):c.7128+2T>A

gnomAD frequency: 0.00001  dbSNP: rs1049504575
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001390237 SCV001591904 pathogenic Spastic paraplegia 2023-11-06 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 38 of the ZFYVE26 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (no rsID available, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with hereditary spastic paraplegia (PMID: 19805727). ClinVar contains an entry for this variant (Variation ID: 551226). Studies have shown that disruption of this splice site results in skipping of exon 38 and introduces a premature termination codon (PMID: 19805727). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV000666227 SCV002060239 likely pathogenic Hereditary spastic paraplegia 15 2021-11-12 criteria provided, single submitter clinical testing NM_015346.3(ZFYVE26):c.7128+2T>A is a canonical splice site variant classified as likely pathogenic in the context of spastic paraplegia type 15. c.7128+2T>A has been observed in a case with relevant disease (PMID: 19805727). Functional assessments of this variant are available in the literature (PMID: 19805727). c.7128+2T>A has been observed in population frequency databases (gnomAD: NFE 0.001%). In summary, NM_015346.3(ZFYVE26):c.7128+2T>A is a canonical splice site variant in a gene where loss of function is a known mechanism of disease, is predicted to disrupt protein function, and has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.

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