MAN2C1 was first reported in relation to autosomal recessive congenital disorder of deglycosylation 2 in 2022 (Maia et al., PMID 35045343). Five variants (missense, frameshift, splice site) that have been reported in 4 probands in 1 publication (PMID 35045343) are included in this curation. Patients have a range of symptoms, including dysmorphic facies, impaired intellectual development, and brain anomalies. The disease mechanism appears to be biallelic loss of function. Heterozygous carriers are reportedly unaffected. As there are specific splice site and LOF variants present in GnomAD in homozygous state (including c.2303G>A and c.601-2A>G and 15-75364145-GTGTAC-G) there is a possibility of reduced penetrance for this condition. This gene-disease relationship is also supported by in vitro assays showing a deficiency in free oligosaccharide processing (PMIDs 35045343, 16848760) as well as a mouse model (PMID 24550399). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Congenital Disorder of Glycosylation GCEP on the meeting date November 7, 2024 (SOP Version 10).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.