ClinVar Genomic variation as it relates to human health
NM_152490.5(B3GALNT2):c.824_825dup (p.Ile276fs)
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_152490.5(B3GALNT2):c.824_825dup (p.Ile276fs)
Variation ID: 132981 Accession: VCV000132981.18
- Type and length
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Duplication, 2 bp
- Location
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Cytogenetic: 1q42.3 1: 235465651-235465652 (GRCh38) [ NCBI UCSC ] 1: 235628968-235628969 (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 Jun 9, 2014 Mar 5, 2024 Feb 28, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_152490.5:c.824_825dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_689703.1:p.Ile276fs frameshift NM_001277155.3:c.947_948dup NP_001264084.1:p.Ile317fs frameshift NM_152490.2:c.824_825dupTT NM_152490.4:c.824_825dup NC_000001.11:g.235465654_235465655dup NC_000001.10:g.235628971_235628972dup NG_033219.2:g.43829_43830dup - Protein change
- I317fs, I276fs
- Other names
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- Canonical SPDI
- NC_000001.11:235465651:AAAA:AAAAAA
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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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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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B3GALNT2 | - | - |
GRCh38 GRCh38 GRCh37 |
440 | 658 |
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 (3) |
criteria provided, single submitter
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Aug 24, 2023 | RCV000119390.6 | |
Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Feb 28, 2024 | RCV000625390.16 |
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
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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
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
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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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Pathogenic
(Oct 12, 2017)
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criteria provided, single submitter
Method: clinical testing
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000745854.1 First in ClinVar: Apr 20, 2018 Last updated: Apr 20, 2018 |
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Pathogenic
(Mar 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003923305.1
First in ClinVar: May 13, 2023 Last updated: May 13, 2023 |
Comment:
Variant summary: B3GALNT2 c.824_825dupTT (p.Ile276LeufsX26) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: B3GALNT2 c.824_825dupTT (p.Ile276LeufsX26) 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. The variant allele was found at a frequency of 0.00021 in 251380 control chromosomes (gnomAD). c.824_825dupTT has been reported in the literature in the compound heterozygous state in individuals affected with and/or with features of Muscular Dystrophy-Dystroglycanopathy (congenital With Brain And Eye Anomalies) and in two siblings presenting with mild intellectual disability and behavioral problems but without muscular involvement (e.g. Stevens_2013, Maroofian_2017, Marangoni_2022). These data indicate that the variant is likely to be associated with disease. A publication reporting experimental evidence evaluating an impact on protein function found the variant failed to restore IIH6 staining in a complementation assay, resulting in <10% of WT activity (Maroofian_2017). Five submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic (n=4)/likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Aug 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000568240.5
First in ClinVar: Jun 09, 2014 Last updated: Aug 31, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 29273094, 35456500, 31980526, 34906519, 23453667) (less)
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Pathogenic
(Jan 28, 2024)
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criteria provided, single submitter
Method: clinical testing
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000826128.6
First in ClinVar: Oct 10, 2018 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ile276Leufs*26) in the B3GALNT2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Ile276Leufs*26) in the B3GALNT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in B3GALNT2 are known to be pathogenic (PMID: 23453667). This variant is present in population databases (rs367543075, gnomAD 0.04%). This premature translational stop signal has been observed in individual(s) with congenital muscular dystrophy and/or congenital muscular dystrophy-dystroglycanopathy (PMID: 23453667, 29273094). It has also been observed to segregate with disease in related individuals. This variant is also known as c.822_823dup. ClinVar contains an entry for this variant (Variation ID: 132981). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Feb 28, 2024)
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criteria provided, single submitter
Method: clinical testing
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV004697571.1
First in ClinVar: Mar 05, 2024 Last updated: Mar 05, 2024 |
Comment:
second B3GALNT2 in trans (Missense-Variant, VUS)
Clinical Features:
Global developmental delay (present) , Elevated circulating creatine kinase concentration (present) , Secondary microcephaly (present)
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Likely pathogenic
(May 31, 2017)
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criteria provided, single submitter
Method: clinical testing
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000745211.1 First in ClinVar: Apr 20, 2018 Last updated: Apr 20, 2018 |
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Pathogenic
(Sep 05, 2019)
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criteria provided, single submitter
Method: clinical testing
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002025106.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001963010.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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not provided
(-)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
germline,
unknown
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Leiden Muscular Dystrophy pages (B3GALNT2)
Accession: SCV000154297.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
has functional consequence
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Observation 1: Observation 2: |
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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Implementation of fetal clinical exome sequencing: Comparing prospective and retrospective cohorts. | Marangoni M | Genetics in medicine : official journal of the American College of Medical Genetics | 2022 | PMID: 34906519 |
B3GALNT2 mutations associated with non-syndromic autosomal recessive intellectual disability reveal a lack of genotype-phenotype associations in the muscular dystrophy-dystroglycanopathies. | Maroofian R | Genome medicine | 2017 | PMID: 29273094 |
Mutations in B3GALNT2 cause congenital muscular dystrophy and hypoglycosylation of α-dystroglycan. | Stevens E | American journal of human genetics | 2013 | PMID: 23453667 |
Text-mined citations for rs367543075 ...
HelpRecord last updated Mar 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.