Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000409222 | SCV000485783 | likely pathogenic | Deficiency of alpha-mannosidase | 2016-02-12 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000409222 | SCV000915814 | uncertain significance | Deficiency of alpha-mannosidase | 2017-08-21 | criteria provided, single submitter | clinical testing | The MAN2B1 c.159+2T>C variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. A literature search was performed for the gene and cDNA change. No publications were found based on this search. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of splice donor variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for alpha-mannosidosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Genome- |
RCV000409222 | SCV001810487 | likely pathogenic | Deficiency of alpha-mannosidase | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000409222 | SCV004402084 | likely pathogenic | Deficiency of alpha-mannosidase | 2022-12-31 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 370454). This variant has not been reported in the literature in individuals affected with MAN2B1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 1 of the MAN2B1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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). |