Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002650898 | SCV003515671 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-05-20 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SKI-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Studies have shown that disruption of this splice site is associated with altered splicing resulting in unknown protein product impact (PMID: 32123317). This variant is present in population databases (rs762589753, gnomAD 0.002%). This sequence change affects a donor splice site in intron 3 of the SKI 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), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SKI cause disease. |