ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.2278C>T (p.Arg760Ter) (rs121434331)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000001753 SCV000220559 likely pathogenic Deficiency of alpha-mannosidase 2014-07-30 criteria provided, single submitter literature only
Integrated Genetics/Laboratory Corporation of America RCV000001753 SCV000697260 pathogenic Deficiency of alpha-mannosidase 2017-03-02 criteria provided, single submitter clinical testing Variant summary: The MAN2B1 c.2278C>T (p.Arg760X) variant results in a premature termination codon, predicted to cause a truncated or absent MAN2B1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 2/108116 (1/54058), which does not exceed the estimated maximal expected allele frequency for a pathogenic MAN2B1 variant of 1/632. A publication, Godota_1998, cites the variant in a sibling pair, where both sisters were homozygous for the variant. Authors indicate that the variant causes a Lysosomal alpha-mannosidosis type 2, with a milder phenotype, hypothesized by "The nonsense mutation in the alpha-mannosidase gene is located in exon 19, at a point ~75% along the length of the protein. This nonsense mutation likely encodes an unstable mRNA, such that a relatively stable but defective protein is produced that can show partial activity toward alpha-mannose residues in vivo." In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as pathogenic.
OMIM RCV000001753 SCV000021909 pathogenic Deficiency of alpha-mannosidase 1998-10-01 no assertion criteria provided literature only

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