ClinVar Genomic variation as it relates to human health
NM_001844.5(COL2A1):c.2862C>T (p.Gly954=)
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_001844.5(COL2A1):c.2862C>T (p.Gly954=)
Variation ID: 988535 Accession: VCV000988535.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 12q13.11 12: 47978630 (GRCh38) [ NCBI UCSC ] 12: 48372413 (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 11, 2020 Mar 10, 2024 Nov 25, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001844.5:c.2862C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001835.3:p.Gly954= synonymous NM_033150.3:c.2655C>T NP_149162.2:p.Gly885= synonymous NC_000012.12:g.47978630G>A NC_000012.11:g.48372413G>A NG_008072.1:g.30873C>T - Protein change
- Other names
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- Canonical SPDI
- NC_000012.12:47978629: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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Allele frequency
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The frequency of the allele represented by this VCV record.
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- 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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COL2A1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2801 | 2814 |
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 (6) |
criteria provided, multiple submitters, no conflicts
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Nov 25, 2023 | RCV001269946.18 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 9, 2022 | RCV002294450.3 |
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
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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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Pathogenic
(Oct 17, 2017)
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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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Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001450321.1
First in ClinVar: Dec 11, 2020 Last updated: Dec 11, 2020 |
Number of individuals with the variant: 2
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Pathogenic
(Feb 04, 2020)
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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: SCV001811906.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
Non-canonical splice site variant demonstrated to result in loss-of-function (Richards et al., 2010); This variant is associated with the following publications: (PMID: 20513134, 26443184, 27193475, … (more)
Non-canonical splice site variant demonstrated to result in loss-of-function (Richards et al., 2010); This variant is associated with the following publications: (PMID: 20513134, 26443184, 27193475, 31781920, 20179744) (less)
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Likely pathogenic
(Sep 30, 2022)
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criteria provided, single submitter
Method: clinical testing
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Stickler syndrome type 1
Affected status: yes
Allele origin:
maternal
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV002587077.1
First in ClinVar: Oct 29, 2022 Last updated: Oct 29, 2022 |
Comment:
_x000D_ Criteria applied: PS3, PS4_MOD, PM2_SUP, PP3, PP4
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Pathogenic
(Dec 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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Stickler syndrome type 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Institute Of Human Genetics Munich, Klinikum Rechts Der Isar, Tu München
Accession: SCV004045906.1
First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023 |
Number of individuals with the variant: 1
Clinical Features:
Pectus excavatum (present) , Cataract (present) , Joint laxity (present) , Cleft palate (present) , Retinal detachment (present) , Myopia (present)
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Pathogenic
(Nov 25, 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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Invitae
Accession: SCV001574302.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects codon 954 of the COL2A1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid … (more)
This sequence change affects codon 954 of the COL2A1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the COL2A1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with clinical features of Stickler syndrome (PMID: 20179744, 20513134). ClinVar contains an entry for this variant (Variation ID: 988535). Studies have shown that this variant alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 20179744, 20513134). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jun 01, 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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004033201.4
First in ClinVar: Sep 16, 2023 Last updated: Mar 10, 2024 |
Comment:
COL2A1: PVS1, PS4:Moderate, PM2:Supporting, PP1, PS3:Supporting
Number of individuals with the variant: 1
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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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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808400.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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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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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: SCV001956980.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 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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Stickler syndrome and the vitreous phenotype: mutations in COL2A1 and COL11A1. | Richards AJ | Human mutation | 2010 | PMID: 20513134 |
Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients. | Hoornaert KP | European journal of human genetics : EJHG | 2010 | PMID: 20179744 |
Text-mined citations for rs367806541 ...
HelpRecord last updated Mar 11, 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.