Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001317549 | SCV001508218 | uncertain significance | Beta-D-mannosidosis | 2022-04-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys849Aspfs*16) in the MANBA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 31 amino acid(s) of the MANBA protein. This variant is present in population databases (rs749997217, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with MANBA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1018273). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001779154 | SCV002015155 | uncertain significance | not specified | 2023-12-07 | criteria provided, single submitter | clinical testing | Variant summary: MANBA c.2544_2545delGA (p.Lys849AspfsX16) results in a premature termination codon and is predicted to cause a truncation of the encoded protein but is not expected to result in an absence of the protein due to nonsense mediated decay. Variants downstream of this position have not been classified as pathogenic by our laboratory or others in ClinVar and have not been reported as disease-causing in the HGMD database. The variant allele was found at a frequency of 3.2e-05 in 251414 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2544_2545delGA in individuals affected with Beta-Mannosidosis and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |