ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.2046+2T>A (rs748712495)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669117 SCV000793830 likely pathogenic Deficiency of alpha-mannosidase 2017-09-01 criteria provided, single submitter clinical testing
Invitae RCV000669117 SCV001576454 likely pathogenic Deficiency of alpha-mannosidase 2020-05-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 16 of the MAN2B1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs748712495, ExAC 0.03%). This variant has not been reported in the literature in individuals with MAN2B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 553630). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MAN2B1 are known to be pathogenic (PMID: 9915946, 22161967). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV001546799 SCV001766383 pathogenic not provided 2021-06-28 criteria provided, single submitter clinical testing Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 9915946, 16199547, 22161967, 27535533)

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