ClinVar Miner

Submissions for variant NM_005908.4(MANBA):c.1454_1455del (p.Tyr485fs) (rs1188116333)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000001751 SCV000819432 pathogenic Beta-D-mannosidosis 2018-08-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr485Cysfs*27) in the MANBA gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported as homozygous in an individual affected with beta-mannosidosis (PMID: 12468273). It is also known as 1541delAT in the literature. Loss-of-function variants in MANBA are known to be pathogenic (PMID: 9384606, 12468273). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000001751 SCV001482244 pathogenic Beta-D-mannosidosis 2021-02-13 criteria provided, single submitter clinical testing Variant summary: MANBA c.1454_1455delAT (p.Tyr485CysfsX27) 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. The variant allele was found at a frequency of 1.2e-05 in 251448 control chromosomes. c.1454_1455delAT has been reported in the literature in individuals affected with Beta-Mannosidosis and has been subsequently cited by others (example, Bedilu_2002, Huynh_2011, Molho-Pessach_2007, Sabourdy_2009, Riise Stensland_2008). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity in leukocytes and fibroblasts (Bedilu_2002). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic citing one overlapping publication utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000001751 SCV000021907 pathogenic Beta-D-mannosidosis 2002-12-01 no assertion criteria provided literature only

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