Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000484435 | SCV000573864 | likely pathogenic | not provided | 2017-03-02 | criteria provided, single submitter | clinical testing | The c.84-1G>A variant in the CLN6 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 acceptor site for intron 1. 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.84-1G>A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.84-1G>A variant is a strong candidate for a pathogenic variant; however, the possibility it may be a rare benign variant cannot be excluded. |
Invitae | RCV002525960 | SCV003521720 | likely pathogenic | Neuronal ceroid lipofuscinosis | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 1 of the CLN6 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 CLN6 are known to be pathogenic (PMID: 19135028). This variant is present in population databases (no rsID available, gnomAD 0.006%). Disruption of this splice site has been observed in individual(s) with CLN6 disease (PMID: 35505348). ClinVar contains an entry for this variant (Variation ID: 424086). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |