ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.1503C>A (p.Cys501Ter) (rs886054230)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina 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, Partners HealthCare Personalized 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.

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