ClinVar Miner

Submissions for variant NM_005908.4(MANBA):c.2158-2A>G (rs772852668)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000754553 SCV000917602 pathogenic Beta-D-mannosidosis 2018-03-19 criteria provided, single submitter clinical testing Variant summary: MANBA c.2158-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a 3 acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing (Alkhayat 1998). The variant allele was found at a frequency of 2.4e-05 in 245996 control chromosomes (gnomAD and publications). This frequency is not significantly higher than expected for a pathogenic variant in MANBA causing Beta-Mannosidosis (2.4e-05 vs 1.10e-03), allowing no conclusion about variant significance. c.2158-2A>G has been reported in the literature in individuals affected with Beta-Mannosidosis (Alkhayat 1998). These data indicate that the variant is likely to be associated with disease. 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 pathogenic.
Center for Statistical Genetics, Columbia University RCV000754553 SCV000853291 pathogenic Beta-D-mannosidosis 2018-10-08 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV001261779 SCV001439099 likely pathogenic Hearing impairment no assertion criteria provided research

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