Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001242867 | SCV001415986 | likely pathogenic | Congenital disorder of deglycosylation | 2023-08-10 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 4 of the NGLY1 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 NGLY1 are known to be pathogenic (PMID: 24651605). 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. ClinVar contains an entry for this variant (Variation ID: 967858). Disruption of this splice site has been observed in individual(s) with intellectual disability, hypotonia, and seizures (PMID: 25356970). This variant is present in population databases (rs756045177, gnomAD 0.006%). |
Gene |
RCV001785800 | SCV002028189 | likely pathogenic | not provided | 2021-11-20 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (Lek et al., 2016); Reported in an individual with intellectual disability, hypotonia, and seizures undergoing exome sequencing; the variant was compound heterozygous with a frameshift variant in NGLY1 (Farwell et al., 2015); This variant is associated with the following publications: (PMID: 25356970) |