ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.2249G>A (p.Arg750Gln)

gnomAD frequency: 0.00004  dbSNP: rs373240866
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000714791 SCV000845523 uncertain significance Deficiency of alpha-mannosidase 2018-08-07 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000714791 SCV001805933 uncertain significance Deficiency of alpha-mannosidase 2021-07-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000714791 SCV002298176 likely pathogenic Deficiency of alpha-mannosidase 2024-09-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 750 of the MAN2B1 protein (p.Arg750Gln). This variant is present in population databases (rs373240866, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MAN2B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 587572). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MAN2B1 protein function. This variant disrupts the p.Arg750 amino acid residue in MAN2B1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9758606, 9915946, 15035660, 22161967). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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