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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ClinVar Genomic variation as it relates to human health
Help
- Interpretation:
-
Uncertain significance
- Review status:
- criteria provided, multiple submitters, no conflicts
- Submissions:
- 3
- First in ClinVar:
- Dec 6, 2016
- Most recent Submission:
- Feb 7, 2023
- Last evaluated:
- Jul 8, 2022
- Accession:
- VCV000324975.9
- Variation ID:
- 324975
- Description:
- single nucleotide variant
Help
NM_018714.3(COG1):c.2666G>A (p.Arg889Gln)
- Allele ID
- 347146
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 17q25.1
- Genomic location
- 17: 73206754 (GRCh38) GRCh38 UCSC
- 17: 71202893 (GRCh37) GRCh37 UCSC
- HGVS
-
Nucleotide Protein Molecular
consequenceNM_018714.3:c.2666G>A MANE Select NP_061184.1:p.Arg889Gln missense NC_000017.11:g.73206754G>A NC_000017.10:g.71202893G>A NG_008971.1:g.18721G>A - Protein change
- R889Q
- Other names
- -
- Canonical SPDI
- NC_000017.11:73206753:G:A
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- The Genome Aggregation Database (gnomAD) 0.00005
- The Genome Aggregation Database (gnomAD) 0.00003
- NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
- Exome Aggregation Consortium (ExAC) 0.00003
- The Genome Aggregation Database (gnomAD), exomes 0.00004
- Links
- ClinGen: CA8740570
- dbSNP: rs148773959
- VarSome
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Uncertain significance | 2 | criteria provided, multiple submitters, no conflicts | Jul 8, 2022 | RCV000346903.8 | |
| Uncertain significance | 1 | criteria provided, single submitter | Sep 11, 2017 | RCV000514562.2 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Uncertain significance
(Sep 11, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics
Accession: SCV000610641.1
First in ClinVar: Nov 05, 2017 Last updated: Nov 05, 2017 |
|
|
|
Uncertain significance
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
COG1 congenital disorder of glycosylation
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000406296.3
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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
|
|
|
Uncertain significance
(Jul 08, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
COG1 congenital disorder of glycosylation
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002145538.2
First in ClinVar: Mar 28, 2022 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 889 of the COG1 protein (p.Arg889Gln). … (more)
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 889 of the COG1 protein (p.Arg889Gln). This variant is present in population databases (rs148773959, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with COG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 324975). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (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| There are no citations in ClinVar for this variation. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs148773959...
HelpThese 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 Mar 05, 2023