ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.1384_1385GC[2] (p.Arg463fs)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001052217 SCV001216417 pathogenic Deficiency of alpha-mannosidase 2019-12-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg463Profs*53) in the MAN2B1 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individuals with alpha-mannosidosis (PMID: 22161967). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. Loss-of-function variants in MAN2B1 are known to be pathogenic (PMID: 9915946, 22161967). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV001052217 SCV001364016 likely pathogenic Deficiency of alpha-mannosidase 2019-07-16 criteria provided, single submitter clinical testing Variant summary: MAN2B1 c.1388_1389delGC (p.Arg463ProfsX53) 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. The variant was absent in 166008 control chromosomes (gnomAD). c.1388_1389delGC has been reported in the literature in individuals affected with Alpha-Mannosidosis (Rise Stensland_2012, Borgwardt_2015). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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 likely pathogenic.

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