ClinVar Genomic variation as it relates to human health
NM_001849.4(COL6A2):c.1466G>A (p.Arg489Gln)
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_001849.4(COL6A2):c.1466G>A (p.Arg489Gln)
Variation ID: 258316 Accession: VCV000258316.21
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 21q22.3 21: 46121563 (GRCh38) [ NCBI UCSC ] 21: 47541477 (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 Oct 3, 2016 Apr 20, 2024 Mar 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001849.4:c.1466G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001840.3:p.Arg489Gln missense NM_058174.3:c.1466G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_478054.2:p.Arg489Gln missense NM_058175.3:c.1466G>A NP_478055.2:p.Arg489Gln missense NC_000021.9:g.46121563G>A NC_000021.8:g.47541477G>A NG_008675.1:g.28445G>A LRG_476:g.28445G>A LRG_476t1:c.1466G>A LRG_476p1:p.Arg489Gln P12110:p.Arg489Gln - Protein change
- R489Q
- Other names
- -
- Canonical SPDI
- NC_000021.9:46121562:G: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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0.00759 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00585
The Genome Aggregation Database (gnomAD) 0.00627
Trans-Omics for Precision Medicine (TOPMed) 0.00667
1000 Genomes Project 0.00759
1000 Genomes Project 30x 0.00874
The Genome Aggregation Database (gnomAD), exomes 0.00174
Exome Aggregation Consortium (ExAC) 0.00193
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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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COL6A2 | - | - |
GRCh38 GRCh37 |
2021 | 2159 |
Conditions - Germline
Condition
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
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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Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Mar 25, 2024 | RCV000241637.11 | |
Likely benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV000305962.5 | |
Likely benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV000360804.5 | |
Benign (2) |
criteria provided, single submitter
|
Jan 18, 2024 | RCV000526158.14 | |
Benign (3) |
criteria provided, single submitter
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May 3, 2019 | RCV000859406.6 |
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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Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000308258.1
First in ClinVar: Oct 03, 2016 Last updated: Oct 03, 2016 |
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Benign
(Jan 18, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000718412.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
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Benign
(May 03, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000613010.2
First in ClinVar: Oct 03, 2016 Last updated: Jan 18, 2020 |
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Myosclerosis
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000436689.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Collagen VI-related myopathy
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000436690.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Benign
(Jan 18, 2024)
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criteria provided, single submitter
Method: clinical testing
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Bethlem myopathy 1A
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000657108.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
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Likely Benign
(Mar 25, 2024)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004847470.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Arg489Gln variant in COL6A2 is classified as likely benign because it has been identified in 1.9% (1392/75038) of African/African American chromosomes, including 15 total … (more)
The p.Arg489Gln variant in COL6A2 is classified as likely benign because it has been identified in 1.9% (1392/75038) of African/African American chromosomes, including 15 total homozygotes by gnomAD (http://gnomad.broadinstitute.org, v.4.0.0). ACMG/AMP Criteria applied: BS1. (less)
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Likely benign
(-)
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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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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001929921.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001957328.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Likely benign
(-)
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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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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002035443.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
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Likely pathogenic
(Oct 08, 2018)
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Flagged submission
flagged submission
Method: clinical testing
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
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Bethlem myopathy 1A
Affected status: yes
Allele origin:
unknown
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NeuroMeGen, Hospital Clinico Santiago de Compostela
Accession: SCV000882605.1
First in ClinVar: Feb 04, 2019 Last updated: Feb 04, 2019 |
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Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more |
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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Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy. | Lampe AK | Journal of medical genetics | 2005 | PMID: 15689448 |
New molecular mechanism for Ullrich congenital muscular dystrophy: a heterozygous in-frame deletion in the COL6A1 gene causes a severe phenotype. | Pan TC | American journal of human genetics | 2003 | PMID: 12840783 |
Text-mined citations for rs61735828 ...
HelpRecord last updated Jun 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.