ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.2401G>T (p.Gly801Cys)

gnomAD frequency: 0.00030  dbSNP: rs142702682
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mayo Clinic Laboratories, Mayo Clinic RCV000660542 SCV000782647 uncertain significance Deficiency of alpha-mannosidase 2017-05-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000660542 SCV001287689 uncertain significance Deficiency of alpha-mannosidase 2018-01-12 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 RCV000660542 SCV001412173 uncertain significance Deficiency of alpha-mannosidase 2022-09-27 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 801 of the MAN2B1 protein (p.Gly801Cys). This variant is present in population databases (rs142702682, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. 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: 547954). Advanced 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 at Invitae 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. 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 RCV000660542 SCV002027037 uncertain significance Deficiency of alpha-mannosidase 2021-09-05 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000660542 SCV002775142 uncertain significance Deficiency of alpha-mannosidase 2022-04-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV002532017 SCV003557036 uncertain significance Inborn genetic diseases 2021-06-04 criteria provided, single submitter clinical testing The c.2401G>T (p.G801C) alteration is located in exon 20 (coding exon 20) of the MAN2B1 gene. This alteration results from a G to T substitution at nucleotide position 2401, causing the glycine (G) at amino acid position 801 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Preventiongenetics, part of Exact Sciences RCV003420157 SCV004117187 uncertain significance MAN2B1-related condition 2023-05-05 criteria provided, single submitter clinical testing The MAN2B1 c.2401G>T variant is predicted to result in the amino acid substitution p.Gly801Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.10% of alleles in individuals of European (Finnish) descent in gnomAD, including one homozygous individual (http://gnomad.broadinstitute.org/variant/19-12759985-C-A), which may be too common to be causative. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV000660542 SCV002086904 uncertain significance Deficiency of alpha-mannosidase 2019-11-11 no assertion criteria provided clinical testing

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