ClinVar Genomic variation as it relates to human health
NM_080680.3(COL11A2):c.4652G>A (p.Arg1551Gln)
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); Likely benign(5)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_080680.3(COL11A2):c.4652G>A (p.Arg1551Gln)
Variation ID: 198337 Accession: VCV000198337.43
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6p21.32 6: 33165647 (GRCh38) [ NCBI UCSC ] 6: 33133424 (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 Apr 15, 2024 Jan 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_080680.3:c.4652G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_542411.2:p.Arg1551Gln missense NM_080679.3:c.4331G>A NP_542410.2:p.Arg1444Gln missense NM_080681.3:c.4394G>A NP_542412.2:p.Arg1465Gln missense NC_000006.12:g.33165647C>T NC_000006.11:g.33133424C>T NG_011589.1:g.31822G>A - Protein change
- R1551Q, R1465Q, R1444Q
- Other names
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- Canonical SPDI
- NC_000006.12:33165646:C:T
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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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0.00020 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD), exomes 0.00049
Exome Aggregation Consortium (ExAC) 0.00058
Trans-Omics for Precision Medicine (TOPMed) 0.00063
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00069
The Genome Aggregation Database (gnomAD) 0.00077
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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COL11A2 | - | - |
GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh37 |
2573 | 2583 |
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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Uncertain significance (1) |
criteria provided, single submitter
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Mar 20, 2017 | RCV000218581.14 | |
Likely benign (1) |
criteria provided, single submitter
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Jun 14, 2016 | RCV000320721.12 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV000377623.12 | |
Likely benign (1) |
criteria provided, single submitter
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Jun 14, 2016 | RCV000381022.12 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV000328722.12 | |
Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
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Jan 29, 2024 | RCV000724415.37 | |
not provided (1) |
no classification provided
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- | RCV003318364.8 |
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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Weissenbacher-Zweymuller Syndrome
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000462255.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Likely benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Stickler Syndrome, Dominant
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000462251.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Uncertain significance
(Oct 13, 2017)
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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: SCV000231896.5
First in ClinVar: Jun 29, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Uncertain significance
(Mar 20, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000271605.2
First in ClinVar: May 29, 2016 Last updated: Apr 09, 2018 |
Comment:
Variant classified as Uncertain Significance - Favor Benign. The p.Arg1551Gln va riant in COL11A2 has been reported by our laboratory in one individual with hear … (more)
Variant classified as Uncertain Significance - Favor Benign. The p.Arg1551Gln va riant in COL11A2 has been reported by our laboratory in one individual with hear ing loss. It has also been reported in ClinVar (Variation ID# 198337) as likely benign or of uncertain significance. This variant has been identified in 0.1% (6 7/66340) of European chromosomes by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org; dbSNP rs145343609). Although this variant has been s een in the general population, its frequency is not high enough to rule out a pa thogenic role. Arginine (Arg) at position 1551 is not conserved in 1 mammal (ten rec) or evolutionarily distant species, supporting that a change at this positio n may be tolerated. Computational prediction tools do not provide strong support for or against an impact to the protein; however, splice prediction tools do su ggest an impact to splicing. In summary, while the clinical significance of the p.Arg1551Gln variant is uncertain, the frequency and conservation data suggest i t is more likely to be benign. (less)
Number of individuals with the variant: 2
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Fibrochondrogenesis 2
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000462252.3
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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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Otospondylomegaepiphyseal dysplasia, autosomal recessive
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000462254.3
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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Uncertain significance
(Jul 25, 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: SCV000573635.7
First in ClinVar: Dec 06, 2016 Last updated: Aug 05, 2023 |
Comment:
Has not been previously published as pathogenic or benign to our knowledge; Observed with a likely pathogenic variant on the opposite allele (in trans) in … (more)
Has not been previously published as pathogenic or benign to our knowledge; Observed with a likely pathogenic variant on the opposite allele (in trans) in a patient with a reported history of connective tissue disease referred for genetic testing at GeneDx; At the protein level, in silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. (less)
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Uncertain significance
(Jun 30, 2021)
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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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Revvity Omics, Revvity
Accession: SCV003831159.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Likely benign
(Jan 29, 2024)
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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: SCV001665133.4
First in ClinVar: Jun 08, 2021 Last updated: Feb 20, 2024 |
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Uncertain significance
(Mar 01, 2019)
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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: SCV001154712.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 2
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not provided
(-)
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no classification provided
Method: phenotyping only
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COL11A2-Related Disorder
Affected status: unknown
Allele origin:
unknown
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GenomeConnect - Brain Gene Registry
Accession: SCV004012811.1
First in ClinVar: Jul 16, 2023 Last updated: Jul 16, 2023 |
Comment:
Variant interpreted as Uncertain significance and reported on 06-14-2021 by Lab The Children's Hospital of Philadelphia. Assertions are reported exactly as they appear on the … (more)
Variant interpreted as Uncertain significance and reported on 06-14-2021 by Lab The Children's Hospital of Philadelphia. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne?from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. (less)
Clinical Features:
Neurodevelopmental delay (present) , Hypoglycemia (present) , Protein-losing enteropathy (present)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: male
Method: Exome Sequencing
Testing laboratory: Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Date variant was reported to submitter: 2021-06-14
Testing laboratory interpretation: Uncertain significance
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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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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=COL11A2 | - | - | - | - |
Text-mined citations for rs145343609 ...
HelpRecord last updated May 01, 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.