Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000697778 | SCV000826407 | likely pathogenic | GRN-related frontotemporal lobar degeneration with Tdp43 inclusions; Neuronal ceroid lipofuscinosis 11 | 2022-07-26 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 9 of the GRN 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 GRN are known to be pathogenic (PMID: 16862116, 16950801, 22608501). Disruption of this splice site has been observed in individual(s) with frontotemporal dementia (PMID: 16862116). ClinVar contains an entry for this variant (Variation ID: 98163). 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. |
VIB Department of Molecular Genetics, |
RCV000084466 | SCV000116602 | not provided | not provided | no assertion provided | not provided |