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
NM_004082.5(DCTN1):c.586A>G (p.Ile196Val)
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.
(12)
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.
Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(6); Likely benign(1)
Uncertain significance(1); Benign(6); Likely benign(1)
12
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_004082.5(DCTN1):c.586A>G (p.Ile196Val)
Variation ID: 337096 Accession: VCV000337096.56
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 2p13.1 2: 74371596 (GRCh38) [ NCBI UCSC ] 2: 74598723 (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 Dec 6, 2016 Oct 20, 2024 Jun 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004082.5:c.586A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004073.2:p.Ile196Val missense NM_001135040.3:c.526A>G NP_001128512.1:p.Ile176Val missense NM_001135041.3:c.184A>G NP_001128513.1:p.Ile62Val missense NM_001190836.2:c.475A>G NP_001177765.1:p.Ile159Val missense NM_001190837.2:c.565A>G NP_001177766.1:p.Ile189Val missense NM_001378991.1:c.535A>G NP_001365920.1:p.Ile179Val missense NM_001378992.1:c.517A>G NP_001365921.1:p.Ile173Val missense NM_023019.4:c.184A>G NP_075408.1:p.Ile62Val missense NR_033935.2:n.566A>G non-coding transcript variant NC_000002.12:g.74371596T>C NC_000002.11:g.74598723T>C NG_008735.2:g.25492A>G LRG_237:g.25492A>G LRG_237t1:c.586A>G LRG_237p1:p.Ile196Val Q14203:p.Ile196Val - Protein change
- I159V, I196V, I62V, I189V, I176V, I173V, I179V
- Other names
- -
- Canonical SPDI
- NC_000002.12:74371595:T:C
-
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.
-
0.00319 (C)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 30x 0.00312
1000 Genomes Project 0.00319
The Genome Aggregation Database (gnomAD), exomes 0.00460
The Genome Aggregation Database (gnomAD) 0.00462
Trans-Omics for Precision Medicine (TOPMed) 0.00483
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00546
Exome Aggregation Consortium (ExAC) 0.00799
- 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. |
|||
| DCTN1 | - | - |
GRCh38 GRCh37 |
1302 | 1318 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Sep 9, 2020 | RCV001260196.11 | |
| Benign (2) |
criteria provided, single submitter
|
Jan 12, 2018 | RCV000333493.14 | |
| Benign (1) |
criteria provided, single submitter
|
Jan 12, 2018 | RCV000380851.13 | |
| Benign (2) |
criteria provided, single submitter
|
Mar 10, 2017 | RCV000507449.14 | |
| Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Jun 1, 2024 | RCV000541293.42 | |
| Benign (1) |
criteria provided, single submitter
|
Jan 29, 2024 | RCV001084399.16 |
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. |
|
|---|---|---|---|---|---|
|
Benign
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Neuronopathy, distal hereditary motor, type 7B
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000432056.3
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
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Perry syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000432055.3
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 10, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000613071.1
First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
|
|
|
Uncertain significance
(Sep 09, 2020)
|
criteria provided, single submitter
Method: case-control
|
Amyotrophic lateral sclerosis
Affected status: yes
Allele origin:
unknown
|
UM ALS/MND Lab, University Of Malta
Accession: SCV001437165.1
First in ClinVar: Oct 07, 2020 Last updated: Oct 07, 2020
Comment:
Single heterozygote
|
Number of individuals with the variant: 1
Age: 50-59 years
Sex: male
Ethnicity/Population group: Maltese
Geographic origin: Malta
|
|
|
Benign
(Sep 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603293.6
First in ClinVar: Sep 30, 2017 Last updated: Feb 20, 2024 |
|
|
|
Benign
(Jan 29, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Amyotrophic lateral sclerosis type 1
Neuronopathy, distal hereditary motor, type 7B Perry syndrome
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000644826.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
|
|
|
Likely benign
(Jun 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001152368.27
First in ClinVar: Feb 03, 2020 Last updated: Oct 20, 2024 |
Comment:
DCTN1: BS2
Number of individuals with the variant: 13
|
|
|
Benign
(Dec 28, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001950536.2
First in ClinVar: Oct 02, 2021 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 23143281, 25382069)
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001922346.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001926773.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001967080.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
|
Uncertain significance
(Jan 06, 2016)
|
no assertion criteria provided
Method: literature only
|
Perry syndrome
Affected status: yes
Allele origin:
germline
|
Inherited Neuropathy Consortium Ii, University Of Miami
Accession: SCV004174488.1
First in ClinVar: Dec 09, 2023 Last updated: Dec 09, 2023 |
|
|
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Comment:
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 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.
Comment:
DCTN1: BS2
Comment:
This variant is associated with the following publications: (PMID: 23143281, 25382069)
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:
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.
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 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.
Comment:
DCTN1: BS2
Comment:
This variant is associated with the following publications: (PMID: 23143281, 25382069)
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Expansion of the classification of FTLD-TDP: distinct pathology associated with rapidly progressive frontotemporal degeneration. | Lee EB | Acta neuropathologica | 2017 | PMID: 28130640 |
| DCTN1 p.K56R in progressive supranuclear palsy. | Gustavsson EK | Parkinsonism & related disorders | 2016 | PMID: 27132499 |
| A human laterality disorder caused by a homozygous deleterious mutation in MMP21. | Perles Z | Journal of medical genetics | 2015 | PMID: 26429889 |
| Amyotrophic lateral sclerosis onset is influenced by the burden of rare variants in known amyotrophic lateral sclerosis genes. | Cady J | Annals of neurology | 2015 | PMID: 25382069 |
| The dynactin p150 subunit: cell biology studies of sequence changes found in ALS/MND and Parkinsonian syndromes. | Stockmann M | Journal of neural transmission (Vienna, Austria : 1996) | 2013 | PMID: 23143281 |
| Tubulin-binding cofactor B is a direct interaction partner of the dynactin subunit p150(Glued). | Kuh GF | Cell and tissue research | 2012 | PMID: 22777741 |
| Characterization of DCTN1 genetic variability in neurodegeneration. | Vilariño-Güell C | Neurology | 2009 | PMID: 19506225 |
| The p150 subunit of dynactin (DCTN1) gene in multiple sclerosis. | Münch C | Acta neurologica Scandinavica | 2007 | PMID: 17824900 |
Text-mined citations for rs55862001 ...
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 19, 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.