Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781513 | SCV000919600 | pathogenic | Deficiency of alpha-mannosidase | 2018-02-12 | criteria provided, single submitter | clinical testing | Variant summary: MAN2B1 c.562C>T (p.Arg188X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.1383C>G, p.Tyr461X; c.2278C>T, p.Arg760X). The variant allele was found at a frequency of 8.6e-06 in 116120 control chromosomes in ExAC and literature. c.562C>T has been reported in the literature in individuals affected with Alpha-Mannosidosis (Sbaragli_2005). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV000781513 | SCV001581393 | pathogenic | Deficiency of alpha-mannosidase | 2021-06-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with alpha-mannosidosis (PMID: 15712269). ClinVar contains an entry for this variant (Variation ID: 633292). This variant is present in population databases (rs1429239930, ExAC 0.006%). This sequence change creates a premature translational stop signal (p.Arg188*) in the MAN2B1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MAN2B1 are known to be pathogenic (PMID: 9915946, 22161967). |
Genome- |
RCV000781513 | SCV002014511 | pathogenic | Deficiency of alpha-mannosidase | 2021-09-05 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003106059 | SCV003761623 | pathogenic | not provided | 2022-07-27 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 15712269) |
Baylor Genetics | RCV000781513 | SCV004191856 | pathogenic | Deficiency of alpha-mannosidase | 2023-10-02 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000781513 | SCV002086943 | pathogenic | Deficiency of alpha-mannosidase | 2021-10-13 | no assertion criteria provided | clinical testing |