Submissions for variant NM_138459.5(NUS1):c.692-2A>G

dbSNP: rs2114693876

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centogene AG - the Rare Disease Company	RCV001809277	SCV002059788	likely pathogenic	Intellectual disability, autosomal dominant 55, with seizures	2021-05-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001869602	SCV002248369	likely pathogenic	Congenital disorder of glycosylation, type IAA	2021-09-26	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with NUS1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 3 of the NUS1 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 NUS1 are known to be pathogenic (PMID: 29100083).