Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001375578 | SCV001572473 | likely pathogenic | MAN2B2-related disorder | 2021-04-09 | criteria provided, single submitter | clinical testing | Variant summary: MAN2B2 c.112G>A (p.Asp38Asn) results in a conservative amino acid change located in the Glycoside hydrosylase family 38, N-terminal domain (IPR000602) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00029 in 199310 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in MAN2B2 causing MAN2B2-Related Disorders, allowing no conclusion about variant significance. c.112G>A has been reported in the literature as a homozygous occurrence in at-least one individual affected with a MAN2B2-Related Disorder, specifically presenting as a congenital disorder of glycosylation (CDG). This individual was from a consanguineous family and the variant segregated with disease as obligate carrier parents and carrier siblings were unaffected (Verheijen_2020). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in a loss of cellular N-glycosylation in patient fibroblasts that was rescued upon induction of wild-type protein (Verheihen_2020). These findings were also supported by characteristic N-linked and free glycan profiles demonstrating an accumulation of Man2GlcNac2 glycans, consistent with defective glycoprotein degradation. 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. |
| Center for Genomic Medicine, |
RCV002287500 | SCV004806271 | uncertain significance | not provided | 2024-03-25 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV002287500 | SCV001423532 | uncertain significance | not provided | 2020-07-16 | no assertion criteria provided | literature only |