ClinVar Genomic variation as it relates to human health
NM_000528.4(MAN2B1):c.1687G>T (p.Glu563Ter)
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.1687G>T (p.Glu563Ter)
Variation ID: 370997 Accession: VCV000370997.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.13 19: 12655837 (GRCh38) [ NCBI UCSC ] 19: 12766651 (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 Jan 6, 2017 Feb 14, 2024 Sep 6, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000528.4:c.1687G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000519.2:p.Glu563Ter nonsense NM_001173498.2:c.1684G>T NP_001166969.1:p.Glu562Ter nonsense NC_000019.10:g.12655837C>A NC_000019.9:g.12766651C>A NG_008318.1:g.15941G>T - Protein change
- E563*, E562*
- Other names
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- Canonical SPDI
- NC_000019.10:12655836:C:A
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD), exomes 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- Links
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 |
1562 | 1738 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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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Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Sep 6, 2023 | RCV000409235.15 |
Submissions - Germline
Classification
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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
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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
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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
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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
(Jun 01, 2016)
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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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Counsyl
Accession: SCV000486444.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
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Pathogenic
(Sep 06, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001234841.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this … (more)
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 370997). This premature translational stop signal has been observed in individuals with alpha-mannosidosis (PMID: 9915946, 17979865). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Glu563*) in the MAN2B1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MAN2B1 are known to be pathogenic (PMID: 9915946, 22161967). (less)
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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: SCV002014298.1
First in ClinVar: Nov 12, 2021 Last updated: Nov 12, 2021 |
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Pathogenic
(Aug 22, 2022)
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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: SCV002572226.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
Variant summary: MAN2B1 c.1687G>T (p.Glu563X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: MAN2B1 c.1687G>T (p.Glu563X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 250910 control chromosomes. c.1687G>T has been reported in the literature in multiple individuals affected with Alpha-Mannosidosis (example, Berg_1999, Lyons_2007). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal lysosomal alpha-mannosidosis enzyme activity (Lyons_2007). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Apr 25, 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:
unknown
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Baylor Genetics
Accession: SCV004191890.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Alpha-mannosidosis
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001454354.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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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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Identification of 83 novel alpha-mannosidosis-associated sequence variants: functional analysis of MAN2B1 missense mutations. | Riise Stensland HM | Human mutation | 2012 | PMID: 22161967 |
Early onset alpha-mannosidosis with slow progression in three Hispanic males. | Lyons MJ | Developmental medicine and child neurology | 2007 | PMID: 17979865 |
Spectrum of mutations in alpha-mannosidosis. | Berg T | American journal of human genetics | 1999 | PMID: 9915946 |
Text-mined citations for rs1057516927 ...
HelpRecord last updated Sep 29, 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.