Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001212173 | SCV001383749 | likely pathogenic | Deficiency of alpha-mannosidase | 2019-08-29 | 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MAN2B1 are known to be pathogenic (PMID: 9915946, 22161967). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with MAN2B1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 8 of the MAN2B1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
| 3billion | RCV001212173 | SCV004013661 | pathogenic | Deficiency of alpha-mannosidase | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. The variant is predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported to be associated with MAN2B1 related disorder (ClinVar ID: VCV000942231). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |