Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Clinical Services Laboratory, |
RCV000387844 | SCV000410791 | uncertain significance | Deficiency of alpha-mannosidase | 2017-04-27 | criteria provided, single submitter | clinical testing | The MAN2B1 c.1503C>A (p.Cys501Ter) variant is a stop-gained variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for alpha-mannosidosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Laboratory for Molecular Medicine, |
RCV000387844 | SCV001365917 | likely pathogenic | Deficiency of alpha-mannosidase | 2019-08-19 | criteria provided, single submitter | clinical testing | The p.Cys501X variant in MAN2B1 has not been previously reported in individuals with alpha-mannosidosis and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 501, which is predicted to lead to a truncated or absent protein. Loss of function of the MAN2B1 gene is an established disease mechanism in autosomal recessive alpha-mannosidosis. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive alpha-mannosidosis. ACMG/AMP Criteria applied: PVS1, PM2. |