ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.2867T>G (p.Leu956Arg)

gnomAD frequency: 0.00002  dbSNP: rs768233248
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, 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
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000206896 SCV000243986 uncertain significance Deficiency of alpha-mannosidase 2012-06-07 no assertion criteria provided literature only

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