ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.1109G>A (p.Trp370Ter) (rs786204715)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169531 SCV000221010 likely pathogenic Deficiency of alpha-mannosidase 2015-01-08 criteria provided, single submitter literature only
Integrated Genetics/Laboratory Corporation of America RCV000169531 SCV001337781 pathogenic Deficiency of alpha-mannosidase 2020-01-16 criteria provided, single submitter clinical testing Variant summary: MAN2B1 c.1109G>A (p.Trp370X) 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. This variant also falls at the last nucleotide of exon 8 of the MAN2B1 coding sequence, which is part of the consensus splice site for this exon. Two computational tools predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251334 control chromosomes (gnomAD). The variant, c.1109G>A, has been reported in the literature in two homozygous patients (siblings) affected with Alpha-Mannosidosis (Riise Stensland_2012). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.