Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001251285 | SCV001426819 | likely pathogenic | Deficiency of alpha-mannosidase | 2020-07-24 | criteria provided, single submitter | clinical testing | Variant summary: MAN2B1 c.1929-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes a 5 splicing donor site. Two predict the variant weakens a 5' donor site. Four predict the variant weakens a 3 acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251488 control chromosomes (gnomAD). c.1929-2A>G has been reported in the literature in at least one individual (homozygous) affected with Alpha-Mannosidosis (Stensland_2011). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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 likely pathogenic. |
| Baylor Genetics | RCV001251285 | SCV005060735 | pathogenic | Deficiency of alpha-mannosidase | 2024-01-26 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001251285 | SCV005836952 | likely pathogenic | Deficiency of alpha-mannosidase | 2024-02-10 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 15 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with alpha-mannosidosis (PMID: 22161967). ClinVar contains an entry for this variant (Variation ID: 974961). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |