Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Revvity Omics, |
RCV000206896 | SCV002022750 | likely pathogenic | Deficiency of alpha-mannosidase | 2021-02-01 | criteria provided, single submitter | clinical testing | |
3billion | RCV000206896 | SCV002058756 | uncertain significance | Deficiency of alpha-mannosidase | 2022-01-03 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported to be associated with MAN2B1 related disorder (PMID:22161967, PS1_P). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.933, PP3_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000024, PM2_M). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. |
Invitae | RCV000206896 | SCV003443884 | uncertain significance | Deficiency of alpha-mannosidase | 2022-03-17 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 956 of the MAN2B1 protein (p.Leu956Arg). This variant is present in population databases (rs768233248, gnomAD 0.02%). This missense change has been observed in individual(s) with alpha-mannosidosis (PMID: 22161967). ClinVar contains an entry for this variant (Variation ID: 208280). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects MAN2B1 function (PMID: 21505070). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Baylor Genetics | RCV000206896 | SCV004191855 | likely pathogenic | Deficiency of alpha-mannosidase | 2023-10-05 | criteria provided, single submitter | clinical testing | |
Clin |
RCV000206896 | SCV000243986 | uncertain significance | Deficiency of alpha-mannosidase | 2012-06-07 | no assertion criteria provided | literature only |