ClinVar Genomic variation as it relates to human health
NM_130837.3(OPA1):c.2362C>T (p.Arg788Ter)
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
-
NM_130837.3(OPA1):c.2362C>T (p.Arg788Ter)
Variation ID: 431941 Accession: VCV000431941.8
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 3q29 3: 193658917 (GRCh38) [ NCBI UCSC ] 3: 193376706 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Aug 20, 2017 Feb 14, 2024 Sep 16, 2022 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_130837.3:c.2362C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_570850.2:p.Arg788Ter nonsense NM_001354663.2:c.1828C>T NP_001341592.1:p.Arg610Ter nonsense NM_001354664.2:c.1825C>T NP_001341593.1:p.Arg609Ter nonsense NM_015560.3:c.2197C>T NP_056375.2:p.Arg733Ter nonsense NM_130831.3:c.2089C>T NP_570844.1:p.Arg697Ter nonsense NM_130832.3:c.2143C>T NP_570845.1:p.Arg715Ter nonsense NM_130833.3:c.2200C>T NP_570846.1:p.Arg734Ter nonsense NM_130834.3:c.2251C>T NP_570847.2:p.Arg751Ter nonsense NM_130835.3:c.2254C>T NP_570848.1:p.Arg752Ter nonsense NM_130836.3:c.2308C>T NP_570849.2:p.Arg770Ter nonsense NC_000003.12:g.193658917C>T NC_000003.11:g.193376706C>T NG_011605.1:g.70774C>T LRG_337:g.70774C>T LRG_337t1:c.2197C>T LRG_337p1:p.Arg733Ter LRG_337t2:c.2362C>T - Protein change
- R733*, R788*, R609*, R770*, R610*, R697*, R715*, R734*, R751*, R752*
- Other names
- p.Arg733*
- Canonical SPDI
- NC_000003.12:193658916:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
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 | ||
---|---|---|---|---|---|---|
HI score
Help
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. |
|||
OPA1 | - | - |
GRCh38 GRCh37 |
1234 | 1423 |
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. |
---|---|---|---|---|
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Sep 16, 2022 | RCV000497995.6 | |
Pathogenic (1) |
criteria provided, single submitter
|
- | RCV001526661.1 |
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. |
|
---|---|---|---|---|---|
Pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Autosomal unknown)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447687.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Optic atrophy (present)
Sex: male
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Optic atrophy
Affected status: yes
Allele origin:
de novo
|
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV001737093.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
|
|
Pathogenic
(Sep 27, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000589521.2
First in ClinVar: Aug 20, 2017 Last updated: Aug 20, 2017 |
Comment:
Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 19319978, 19112530, 25525159, 22433900)
|
|
Pathogenic
(May 31, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004226058.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP1, PM2, PS4_supporting, PVS1
Number of individuals with the variant: 1
|
|
Pathogenic
(Sep 16, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV003525573.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 431941). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 431941). This premature translational stop signal has been observed in individual(s) with optic atrophy (PMID: 19112530, 34242285). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg733*) in the OPA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OPA1 are known to be pathogenic (PMID: 11440988, 20157015, 20952381, 25012220). (less)
|
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 |
---|---|---|---|---|
Mutation spectrum of the OPA1 gene in a large cohort of patients with suspected dominant optic atrophy: Identification and classification of 48 novel variants. | Weisschuh N | PloS one | 2021 | PMID: 34242285 |
Identification of copy number variation in the gene for autosomal dominant optic atrophy, OPA1, in a Chinese pedigree. | Jin X | Genetics and molecular research : GMR | 2015 | PMID: 26400325 |
Mutation screening of mitochondrial DNA as well as OPA1 and OPA3 in a Chinese cohort with suspected hereditary optic atrophy. | Chen J | Investigative ophthalmology & visual science | 2014 | PMID: 25205859 |
Early-onset Behr syndrome due to compound heterozygous mutations in OPA1. | Bonneau D | Brain : a journal of neurology | 2014 | PMID: 25012220 |
Standardized mitochondrial analysis gives new insights into mitochondrial dynamics and OPA1 function. | Chevrollier A | The international journal of biochemistry & cell biology | 2012 | PMID: 22433900 |
OPA1 mutations impair mitochondrial function in both pure and complicated dominant optic atrophy. | Yu-Wai-Man P | Brain : a journal of neurology | 2011 | PMID: 20952381 |
Multi-system neurological disease is common in patients with OPA1 mutations. | Yu-Wai-Man P | Brain : a journal of neurology | 2010 | PMID: 20157015 |
Novel mutations of the OPA1 gene in Chinese dominant optic atrophy. | Yen MY | Ophthalmology | 2010 | PMID: 19969356 |
Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations. | Ferré M | Human mutation | 2009 | PMID: 19319978 |
Identification of two novel OPA1 mutations in Chinese families with autosomal dominant optic atrophy. | Li Y | Molecular vision | 2008 | PMID: 19112530 |
OPA1 mutations in patients with autosomal dominant optic atrophy and evidence for semi-dominant inheritance. | Pesch UE | Human molecular genetics | 2001 | PMID: 11440988 |
click to load more click to collapse |
Text-mined citations for rs1553784985 ...
HelpRecord last updated Feb 14, 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.