Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000020366 | SCV001232498 | pathogenic | Deficiency of alpha-mannosidase | 2023-07-30 | criteria provided, single submitter | clinical testing | Studies have shown that disruption of this splice site is associated with altered splicing resulting in multiple RNA products (PMID: 9915946). ClinVar contains an entry for this variant (Variation ID: 21209). Disruption of this splice site has been observed in individuals with alpha-mannosidosis (PMID: 9915946). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 17 of the MAN2B1 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 MAN2B1 are known to be pathogenic (PMID: 9915946, 22161967). This variant disrupts a region of the MAN2B1 protein in which other variant(s) (p.Trp714Arg) have been determined to be pathogenic (PMID: 9915946, 22161967). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000020366 | SCV002014187 | pathogenic | Deficiency of alpha-mannosidase | 2021-09-05 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000020366 | SCV000040753 | not provided | Deficiency of alpha-mannosidase | no assertion provided | literature only |