1-173825336-GT-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_018122.5(DARS2):c.109del(p.Ser37HisfsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
DARS2
NM_018122.5 frameshift
NM_018122.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.635
Genes affected
DARS2 (HGNC:25538): (aspartyl-tRNA synthetase 2, mitochondrial) The protein encoded by this gene belongs to the class-II aminoacyl-tRNA synthetase family. It is a mitochondrial enzyme that specifically aminoacylates aspartyl-tRNA. Mutations in this gene are associated with leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL). [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-173825336-GT-G is Pathogenic according to our data. Variant chr1-173825336-GT-G is described in ClinVar as [Pathogenic]. Clinvar id is 3063594.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DARS2 | NM_018122.5 | c.109del | p.Ser37HisfsTer26 | frameshift_variant | 1/17 | ENST00000649689.2 | |
DARS2 | NM_001365212.1 | c.109del | p.Ser37HisfsTer26 | frameshift_variant | 1/16 | ||
DARS2 | NM_001365213.2 | c.109del | p.Ser37HisfsTer26 | frameshift_variant | 1/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DARS2 | ENST00000649689.2 | c.109del | p.Ser37HisfsTer26 | frameshift_variant | 1/17 | NM_018122.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Department of Human Genetics, Hannover Medical School | Mar 27, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.