Total submissions: 2
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, |
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. |