ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.1668C>A (p.Asp556Glu)

gnomAD frequency: 0.00013  dbSNP: rs766513928
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000292286 SCV000410789 uncertain significance Deficiency of alpha-mannosidase 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000292286 SCV000752983 uncertain significance Deficiency of alpha-mannosidase 2022-07-29 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 556 of the MAN2B1 protein (p.Asp556Glu). This variant is present in population databases (rs766513928, gnomAD 0.03%). 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: 328266). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Genome-Nilou Lab RCV000292286 SCV002027039 uncertain significance Deficiency of alpha-mannosidase 2021-09-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV002521189 SCV003758975 uncertain significance Inborn genetic diseases 2022-12-12 criteria provided, single submitter clinical testing The c.1668C>A (p.D556E) alteration is located in exon 14 (coding exon 14) of the MAN2B1 gene. This alteration results from a C to A substitution at nucleotide position 1668, causing the aspartic acid (D) at amino acid position 556 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000292286 SCV001455937 uncertain significance Deficiency of alpha-mannosidase 2020-01-10 no assertion criteria provided clinical testing

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