ClinVar Genomic variation as it relates to human health
NM_000528.4(MAN2B1):c.2398G>C (p.Gly800Arg)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000528.4(MAN2B1):c.2398G>C (p.Gly800Arg)
Variation ID: 208273 Accession: VCV000208273.5
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.13 19: 12649174 (GRCh38) [ NCBI UCSC ] 19: 12759988 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Feb 2, 2016 Jun 17, 2024 Jan 9, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000528.4:c.2398G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000519.2:p.Gly800Arg missense NM_001173498.2:c.2395G>C NP_001166969.1:p.Gly799Arg missense NC_000019.10:g.12649174C>G NC_000019.9:g.12759988C>G NG_008318.1:g.22604G>C O00754:p.Gly800Arg - Protein change
- G800R, G799R
- Other names
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- Canonical SPDI
- NC_000019.10:12649173:C:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00020 (A)
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MAN2B1 | - | - |
GRCh38 GRCh37 |
1560 | 1735 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jan 9, 2024 | RCV000206964.6 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Sep 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Deficiency of alpha-mannosidase
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002014531.1
First in ClinVar: Nov 12, 2021 Last updated: Nov 12, 2021 |
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Likely pathogenic
(Jun 21, 2023)
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criteria provided, single submitter
Method: clinical testing
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Deficiency of alpha-mannosidase
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004020704.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
Variant summary: MAN2B1 c.2398G>C (p.Gly800Arg) results in a non-conservative amino acid change located in the glycosyl hydrolase family 38, C-terminal domain (IPR011682) of the encoded … (more)
Variant summary: MAN2B1 c.2398G>C (p.Gly800Arg) results in a non-conservative amino acid change located in the glycosyl hydrolase family 38, C-terminal domain (IPR011682) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251404 control chromosomes (gnomAD). c.2398G>C has been reported in the literature in the compound heterozygous state together with a truncating variant in an individual affected with Alpha-Mannosidosis (Riise Stensland_2012, Borgwardt_2015). These data do not allow any conclusion about variant significance. Functional studies have found that the variant has impaired transport to lysosomes, producing a protein that is not intracellularly processed like the WT protein, and it results in <20% activity of the WT enzyme (e.g. Kuokkanen_2011, Riise Stensland_2012, Borgwardt_2015). Additionally, another variant affecting the same amino acid (c.2398G>T, p.G800W) has also been reported in association with Alpha-Mannosidosis in the HGMD database, suggesting Gly800 may be important for protein function. The following publications have been ascertained in the context of this evaluation (PMID: 26048034, 21505070, 22161967). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
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Likely pathogenic
(Jan 09, 2024)
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criteria provided, single submitter
Method: clinical testing
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Deficiency of alpha-mannosidase
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV005060738.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
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Uncertain significance
(Jun 07, 2012)
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no assertion criteria provided
Method: literature only
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Deficiency of alpha-mannosidase
Affected status: yes
Allele origin:
germline
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ClinVar Staff, National Center for Biotechnology Information (NCBI)
Accession: SCV000243979.1
First in ClinVar: Feb 02, 2016 Last updated: Feb 02, 2016 |
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Pathogenic
(Jun 07, 2017)
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no assertion criteria provided
Method: curation
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Deficiency of alpha-mannosidase
Affected status: no
Allele origin:
germline
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SingHealth Duke-NUS Institute of Precision Medicine
Accession: SCV000853118.1
First in ClinVar: Nov 25, 2018 Last updated: Nov 25, 2018 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation. | Borgwardt L | Orphanet journal of rare diseases | 2015 | PMID: 26048034 |
Identification of 83 novel alpha-mannosidosis-associated sequence variants: functional analysis of MAN2B1 missense mutations. | Riise Stensland HM | Human mutation | 2012 | PMID: 22161967 |
Molecular and cellular characterization of novel {alpha}-mannosidosis mutations. | Kuokkanen E | Human molecular genetics | 2011 | PMID: 21505070 |
http://web.expasy.org/variant_pages/VAR_068060.html | - | - | - | - |
Text-mined citations for rs398123456 ...
HelpRecord last updated Sep 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.