ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.2355G>A (p.Thr785=) (rs1008745697)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669668 SCV000794444 likely pathogenic Deficiency of alpha-mannosidase 2017-09-27 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000669668 SCV000919601 pathogenic Deficiency of alpha-mannosidase 2018-03-19 criteria provided, single submitter clinical testing Variant summary: MAN2B1 c.2355G>A (p.Thr785Thr) alters a conserved nucleotide located at the canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5 splicing donor site and three predict the variant creates a 3 acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing (RiseStensland_2012). The variant allele was found at a frequency of 4.1e-06 in 245802 control chromosomes (gnomAD and publications). c.2355G>A has been reported in the literature in individuals affected with Alpha-Mannosidosis (both as compound heterozygotes and one homozygote)(RiseStensland_2012, Borgwardt_2015). 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.

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