ClinVar Genomic variation as it relates to human health
NM_001849.4(COL6A2):c.511G>A (p.Gly171Arg)
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.
Uncertain significance(5); Benign(1); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001849.4(COL6A2):c.511G>A (p.Gly171Arg)
Variation ID: 282184 Accession: VCV000282184.55
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 21q22.3 21: 46112374 (GRCh38) [ NCBI UCSC ] 21: 47532288 (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 Dec 6, 2016 Jun 23, 2024 Mar 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001849.4:c.511G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001840.3:p.Gly171Arg missense NM_058174.3:c.511G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_478054.2:p.Gly171Arg missense NM_058175.3:c.511G>A NP_478055.2:p.Gly171Arg missense NC_000021.9:g.46112374G>A NC_000021.8:g.47532288G>A NG_008675.1:g.19256G>A LRG_476:g.19256G>A LRG_476t1:c.511G>A LRG_476p1:p.Gly171Arg - Protein change
- G171R
- Other names
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- Canonical SPDI
- NC_000021.9:46112373: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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0.00060 (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 0.00055
1000 Genomes Project 0.00060
1000 Genomes Project 30x 0.00062
Exome Aggregation Consortium (ExAC) 0.00107
Trans-Omics for Precision Medicine (TOPMed) 0.00112
The Genome Aggregation Database (gnomAD) 0.00116
The Genome Aggregation Database (gnomAD), exomes 0.00116
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
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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 |
2018 | 2156 |
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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Likely benign (1) |
criteria provided, single submitter
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Jun 14, 2016 | RCV000329881.6 | |
Benign (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV000386454.6 | |
COL6A2-related disorder
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Uncertain significance (2) |
criteria provided, single submitter
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Feb 8, 2023 | RCV000723333.3 |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Mar 1, 2024 | RCV000725047.33 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Jan 19, 2024 | RCV001257054.11 | |
Likely pathogenic (1) |
no assertion criteria provided
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- | RCV002227938.3 |
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 benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Myosclerosis
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000436635.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Uncertain significance
(May 18, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000333499.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 21
Sex: mixed
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Benign
(Jan 12, 2018)
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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
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Illumina Laboratory Services, Illumina
Accession: SCV000436636.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
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 … (more)
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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Uncertain significance
(Oct 06, 2021)
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criteria provided, single submitter
Method: clinical testing
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Bethlem myopathy 1A
Affected status: yes
Allele origin:
unknown
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Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV001976898.1
First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
Comment:
PP2, PP3, BS2
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Uncertain significance
(Jul 26, 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: SCV000568740.6
First in ClinVar: Dec 06, 2016 Last updated: Aug 05, 2023 |
Comment:
Reported previously as a variant of uncertain significance in patients with clinically suspected limb-girdle muscular dystrophy; however, no further clinical or segregation information was provided … (more)
Reported previously as a variant of uncertain significance in patients with clinically suspected limb-girdle muscular dystrophy; however, no further clinical or segregation information was provided (Nallamilli et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24036952, 34803902, 30564623) (less)
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Uncertain significance
(Apr 12, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001713888.2
First in ClinVar: Jun 15, 2021 Last updated: Jan 26, 2024 |
Comment:
BS1
Number of individuals with the variant: 2
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Likely benign
(Jan 19, 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: SCV000657209.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
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Likely benign
(Mar 01, 2024)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001153584.23
First in ClinVar: Feb 03, 2020 Last updated: Jun 17, 2024 |
Comment:
COL6A2: BS1
Number of individuals with the variant: 3
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Uncertain significance
(Feb 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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COL6A2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004114626.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The COL6A2 c.511G>A variant is predicted to result in the amino acid substitution p.Gly171Arg. This variant has been previously observed in a large cohort of … (more)
The COL6A2 c.511G>A variant is predicted to result in the amino acid substitution p.Gly171Arg. This variant has been previously observed in a large cohort of individuals with clinically suspected limb-girdle muscular dystrophy (Table S7, Nallamilli et al. 2018. PubMed ID: 30564623). This variant is reported in 0.23% of alleles in individuals of Ashkenazi Jewish descent in gnomAD, including one homozygote (http://gnomad.broadinstitute.org/variant/21-47532288-G-A). This variant has conflicting interpretations of benign, likely benign, and uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/282184/). 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. (less)
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Uncertain significance
(Jul 18, 2018)
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no assertion criteria provided
Method: clinical testing
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COL6A2-related disorder
Affected status: yes
Allele origin:
germline
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Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Accession: SCV000854730.1
First in ClinVar: Dec 09, 2018 Last updated: Dec 09, 2018 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Tip-toe gait
Affected status: yes
Allele origin:
germline
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Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking c/o Practice Pomarino
Accession: SCV002507279.2
First in ClinVar: May 16, 2022 Last updated: Jun 23, 2024 |
Comment:
Myopathy refers to diseases that affect skeletal Muscles. These diseases attack muscle fibers, making muscles weak. Inherited myopathies are often caused by inheriting an abnormal … (more)
Myopathy refers to diseases that affect skeletal Muscles. These diseases attack muscle fibers, making muscles weak. Inherited myopathies are often caused by inheriting an abnormal gene mutation from a parent that causes the disease. Symptoms of congenital myopathies usually start at birth or in early childhood, but may not appear until the teen years or even later in adulthood. Congenital myopathies are somewhat unique compared with other inherited myopathies, as weakness typically affects all muscles and is often not progressive. Symptoms are: Muscle weakness, most commonly of upper arms and shoulders and thighs, muscle cramps, stiffness and spasms, fatigue with exertion and lack of energy. Our patients all walk on tiptoe, so they show similar symptoms. When we genetically test them with our toe walking panel, we find that around 90 per cent of them have a genetic variant that explains their toe walking. These can be assigned, for example, to the area of myopathies (such as variants of the COL6A3 gene), the area of hereditary neuropathies (such as variants of the KMT2C gene) or the area of metabolic diseases (such as variants of the PYGM gene). In a smaller group of patients with almost identical symptoms, no abnormality is found in the genes of our panel, but spastic paraplegia can be detected. In another small group of our toe walkers, no abnormalities can be detected in the genes analysed in our toe walking panel, nor do they suffer from spastic paraplegia, as is also the case with healthy children. In contrast to these, however, they show a tiptoe gait. These patients suffer from infantile cerebral palsy, in which toe walking can also be observed. (less)
Clinical Features:
Pes cavus (present)
Age: 0-9 years
Sex: female
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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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NGS-Panel Diagnosis Developed for the Differential Diagnosis of Idiopathic Toe Walking and Its Application for the Investigation of Possible Genetic Causes for the Gait Anomaly. | Pomarino D | Global medical genetics | 2023 | PMID: 37091313 |
Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients. | Nallamilli BRR | Annals of clinical and translational neurology | 2018 | PMID: 30564623 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=COL6A2 | - | - | - | - |
Text-mined citations for rs200710788 ...
HelpRecord last updated Jul 07, 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.