The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.
ClinVar Genomic variation as it relates to human health
NM_130837.3(OPA1):c.1389dup (p.Gly464fs)
Germline
Classification
Help
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.
(4)
Help
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.
Pathogenic
4
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_130837.3(OPA1):c.1389dup (p.Gly464fs)
Variation ID: 500848 Accession: VCV000500848.8
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 3q29 3: 193643538-193643539 (GRCh38) [ NCBI UCSC ] 3: 193361327-193361328 (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 Apr 2, 2018 Nov 3, 2024 Apr 23, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_130837.3:c.1389dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_570850.2:p.Gly464fs frameshift NM_001354663.2:c.855dup NP_001341592.1:p.Gly286fs frameshift NM_001354664.2:c.852dup NP_001341593.1:p.Gly285fs frameshift NM_015560.3:c.1224dup NP_056375.2:p.Gly409fs frameshift NM_130831.3:c.1116dup NP_570844.1:p.Gly373fs frameshift NM_130832.3:c.1170dup NP_570845.1:p.Gly391fs frameshift NM_130833.3:c.1227dup NP_570846.1:p.Gly410fs frameshift NM_130834.3:c.1278dup NP_570847.2:p.Gly427fs frameshift NM_130835.3:c.1281dup NP_570848.1:p.Gly428fs frameshift NM_130836.3:c.1335dup NP_570849.2:p.Gly446fs frameshift NC_000003.12:g.193643539dup NC_000003.11:g.193361328dup NG_011605.1:g.55396dup LRG_337:g.55396dup LRG_337t1:c.1224dup LRG_337p1:p.Gly409fs - Protein change
- G285fs, G373fs, G410fs, G428fs, G446fs, G286fs, G391fs, G427fs, G409fs, G464fs
- Other names
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- Canonical SPDI
- NC_000003.12:193643538:A:AA
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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
Help
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
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 |
1269 | 1460 | |
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
|
Apr 23, 2024 | RCV000597597.10 |
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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Pathogenic
(Mar 22, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000706963.2
First in ClinVar: Apr 02, 2018 Last updated: Apr 02, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
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Pathogenic
(Jul 24, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Athena Diagnostics
Accession: SCV001475333.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
Comment:
The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in … (more)
The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data. (less)
|
|
|
Pathogenic
(Mar 09, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003315402.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gly409Argfs*5) in the OPA1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gly409Argfs*5) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 500848). This variant has not been reported in the literature in individuals affected with OPA1-related conditions. This variant is not present in population databases (gnomAD no frequency). (less)
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Pathogenic
(Apr 23, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV005384943.1
First in ClinVar: Nov 03, 2024 Last updated: Nov 03, 2024 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge (less)
|
Comment:
Comment:
This sequence change creates a premature translational stop signal (p.Gly409Argfs*5) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 500848). This variant has not been reported in the literature in individuals affected with OPA1-related conditions. This variant is not present in population databases (gnomAD no frequency).
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
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. |
Comment:
The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.
Comment:
This sequence change creates a premature translational stop signal (p.Gly409Argfs*5) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 500848). This variant has not been reported in the literature in individuals affected with OPA1-related conditions. This variant is not present in population databases (gnomAD no frequency).
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Early-onset Behr syndrome due to compound heterozygous mutations in OPA1. | Bonneau D | Brain : a journal of neurology | 2014 | PMID: 25012220 |
| 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 |
| OPA1 mutations in patients with autosomal dominant optic atrophy and evidence for semi-dominant inheritance. | Pesch UE | Human molecular genetics | 2001 | PMID: 11440988 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=OPA1 | - | - | - | - |
Text-mined citations for rs1553877912 ...
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 Nov 03, 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.