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NM_018122.5(DARS2):c.492+2T>C

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
9 (Most recent: Feb 1, 2019)
Last evaluated:
Mar 14, 2018
Accession:
VCV000001062.3
Variation ID:
1062
Description:
single nucleotide variant
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NM_018122.5(DARS2):c.492+2T>C

Allele ID
16101
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1q25.1
Genomic location
1: 173831632 (GRCh38) GRCh38 UCSC
1: 173800770 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.10:g.173800770T>C
NC_000001.11:g.173831632T>C
NM_018122.5:c.492+2T>C splice donor
... more HGVS
Protein change
-
Other names
IVS5DS, T-C, +2
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00076
Trans-Omics for Precision Medicine (TOPMed) 0.00014
Links
dbSNP: rs142433332
ClinGen: CA208387
OMIM: 610956.0006
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 4 criteria provided, multiple submitters, no conflicts Apr 28, 2017 RCV000001117.8
Pathogenic 2 criteria provided, multiple submitters, no conflicts Mar 14, 2018 RCV000255444.4
Pathogenic 1 criteria provided, single submitter Sep 4, 2014 RCV000194299.1
Pathogenic 1 criteria provided, single submitter Jan 15, 2015 RCV000415333.1
Pathogenic 1 criteria provided, single submitter Jan 1, 2017 RCV000626946.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
DARS2 - - GRCh38
GRCh37
105 134

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Aug 25, 2014)
criteria provided, single submitter
Method: clinical testing
Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation
Allele origin: germline
Courtagen Diagnostics Laboratory,Courtagen Life Sciences
Accession: SCV000236507.2
Submitted: (May 28, 2015)
Evidence details
Pathogenic
(Sep 04, 2014)
criteria provided, single submitter
Method: clinical testing
Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation
Allele origin: germline
Genetic Services Laboratory, University of Chicago
Accession: SCV000247159.1
Submitted: (Sep 15, 2015)
Evidence details
Pathogenic
(Jan 15, 2015)
criteria provided, single submitter
Method: clinical testing
Dysmetria
Gait ataxia
Gait imbalance
Allele origin: unknown
Centre for Mendelian Genomics,University Medical Centre Ljubljana
Accession: SCV000492906.1
Submitted: (Nov 12, 2016)
Evidence details
Pathogenic
(Jan 01, 2017)
criteria provided, single submitter
Method: clinical testing
Abnormality of the foot
CNS demyelination
Cerebral cortical atrophy
Difficulty walking
EMG: axonal abnormality
Gout
Hypertension
Impaired vibration sensation in the lower limbs
Sensorimotor neuropathy
Talipes equinovarus
Allele origin: unknown
Centre for Mendelian Genomics,University Medical Centre Ljubljana
Accession: SCV000747649.1
Submitted: (Dec 08, 2017)
Evidence details
Pathogenic
(Aug 08, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics
Accession: SCV000333003.4
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (2)
Other databases
http://www.egl-eurofins.com/em...
Pathogenic
(Mar 14, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000322293.6
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The c.492+2T>C pathogenic variant in the DARS2 gene has been reported previously in combination with another pathogenic DARS2 variant in multiple unrelated individuals with leukoencephalopathy ... (more)
Pathogenic
(Apr 28, 2017)
criteria provided, single submitter
Method: clinical testing
Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000915374.1
Submitted: (Feb 01, 2019)
Evidence details
Publications
PubMed (7)
Comment:
The DARS2 c.492+2T>C variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. This variant ... (more)
pathologic
(May 25, 2010)
no assertion criteria provided
Method: curation
Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation
Allele origin: not provided
GeneReviews
Accession: SCV000041314.1
Submitted: (Jan 08, 2013)
Evidence details
Comment:
Converted during submission to Pathogenic.
Pathogenic
(Jan 01, 2010)
no assertion criteria provided
Method: literature only
LEUKOENCEPHALOPATHY WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LACTATE ELEVATION
Allele origin: germline
OMIM
Accession: SCV000021267.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (2)

Citations for this variant

Title Author Journal Year Link
Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation van der Knaap MS - 2015 PMID: 20506600
Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation: high outcome variation between two siblings. Tylki-Szymanska A Neuropediatrics 2014 PMID: 24407472
A case with leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate (LBSL) with Its Characteristic Clinical and Neuroimaging Findings. Alibas H Clinical neuroradiology 2014 PMID: 24005482
Impaired information-processing speed and working memory in leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate (LBSL) and DARS2 mutations: a report of three adult patients. Martikainen MH Journal of neurology 2013 PMID: 23652419
Early-onset LBSL: how severe does it get? Steenweg ME Neuropediatrics 2012 PMID: 23065766
Leukoencephalopathy with brain stem and spinal cord involvement (and high lactate): raising the bar for diagnosis. Moore SA Journal of neurology 2012 PMID: 22843165
DARS2 mutations in mitochondrial leucoencephalopathy and multiple sclerosis. Isohanni P Journal of medical genetics 2010 PMID: 19592391
Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Scheper GC Nature genetics 2007 PMID: 17384640
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DARS2 - - - -

Record last updated Oct 27, 2019