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.
ClinVar Genomic variation as it relates to human health
Help
- Interpretation:
-
Benign
- Review status:
- criteria provided, multiple submitters, no conflicts
- Submissions:
- 8
- First in ClinVar:
- Feb 20, 2014
- Most recent Submission:
- Mar 26, 2023
- Last evaluated:
- Oct 31, 2022
- Accession:
- VCV000008390.10
- Variation ID:
- 8390
- Description:
- single nucleotide variant
Help
NM_000557.5(GDF5):c.-275=
- Allele ID
- 23429
- Variant type
- single nucleotide variant
- Variant length
- -
- Cytogenetic location
- 20q11.22
- Genomic location
- 20: 35438203 (GRCh38) GRCh38 UCSC
- 20: 34025983 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000557.5:c.-275= MANE Select no sequence alteration NM_001319138.2:c.-241-34= intron variant NC_000020.11:g.35438203= NC_000020.10:g.34025983A>G NG_008076.3:g.21544= NG_052612.1:g.375= - Protein change
- -
- Other names
- +104T/C (rs143383)
- Canonical SPDI
- NC_000020.11:35438202:G:G
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- Trans-Omics for Precision Medicine (TOPMed) 0.52099
- Trans-Omics for Precision Medicine (TOPMed) 0.52708
- The Genome Aggregation Database (gnomAD) 0.53070
- Links
- ClinGen: CA325631
- OMIM: 601146.0015
- dbSNP: rs143383
- dbSNP: rs1555823599
- VarSome
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Benign | 2 | criteria provided, multiple submitters, no conflicts | Oct 31, 2022 | RCV001520742.6 | |
| Benign | 1 | criteria provided, single submitter | Mar 6, 2018 | RCV000285133.7 | |
| Benign | 1 | criteria provided, single submitter | Mar 6, 2018 | RCV000344695.7 | |
| Benign | 1 | criteria provided, single submitter | Mar 6, 2018 | RCV000290932.7 | |
| Benign | 1 | criteria provided, single submitter | Mar 6, 2018 | RCV000385268.7 | |
| Benign | 1 | criteria provided, single submitter | Mar 6, 2018 | RCV000350530.7 | |
| risk factor | 1 | no assertion criteria provided | Apr 1, 2007 | RCV000008898.6 |
Help
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation viewer | Related variants | ||
|---|---|---|---|---|---|---|
| HI score Help | TS score Help | Within gene | All | |||
| GDF5 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
101 | 244 | |
| LOC109461476 | - | - | - | GRCh38 | - | 23 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Benign
(Mar 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000433744.3
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)
|
|
|
Benign
(Mar 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000433745.3
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)
|
|
|
Benign
(Mar 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000433746.3
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)
|
|
|
Benign
(Mar 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000433743.3
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)
|
|
|
Benign
(Mar 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000433747.3
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)
|
|
|
Benign
(Nov 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001859701.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 22905146, 23825960, 17384641, 24861163, 18299287, 17616513, 18947434, 19565498, 19479880)
|
|
|
Benign
(Oct 31, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001729921.2
First in ClinVar: Jun 15, 2021 Last updated: Mar 26, 2023 |
|
|
|
risk factor
(Apr 01, 2007)
|
no assertion criteria provided
Method: literature only
|
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000029108.3
First in ClinVar: Apr 04, 2013 Last updated: Apr 06, 2020 |
Comment on evidence:
Miyamoto et al. (2007) found significant association (p = 1.8 x 10(-13)) between a SNP in the 5-prime untranslated region (UTR) of GDF5, +104T/C (rs143383), … (more)
Miyamoto et al. (2007) found significant association (p = 1.8 x 10(-13)) between a SNP in the 5-prime untranslated region (UTR) of GDF5, +104T/C (rs143383), and hip osteoarthritis (OS5; 612400) in 2 independent Japanese populations. This association was replicated for knee osteoarthritis in Japanese (p = 0.0021) and Han Chinese (p = 0.00028) populations. This SNP, located in the GDF5 core promoter, exerts allelic differences on transcriptional activity in chondrogenic cells, with the susceptibility allele (T) showing reduced activity. The findings implicated GDF5 as a susceptibility gene for osteoarthritis and suggested that decreased GDF5 expression is involved in the pathogenesis of osteoarthritis. (less)
|
Functional evidence
Help| 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 this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| A functional polymorphism in the 5' UTR of GDF5 is associated with susceptibility to osteoarthritis. | Miyamoto Y | Nature genetics | 2007 | PMID: 17384641 |
Text-mined citations for this variant
Helprs143383: ...
rs1555823599: ...
These citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 16, 2023