1-173828364-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_018122.5(DARS2):c.259G>A(p.Asp87Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,608,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D87G) has been classified as Likely benign.
Frequency
Consequence
NM_018122.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DARS2 | NM_018122.5 | c.259G>A | p.Asp87Asn | missense_variant | 3/17 | ENST00000649689.2 | |
DARS2 | NM_001365212.1 | c.259G>A | p.Asp87Asn | missense_variant | 3/16 | ||
DARS2 | NM_001365213.2 | c.259G>A | p.Asp87Asn | missense_variant | 3/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DARS2 | ENST00000649689.2 | c.259G>A | p.Asp87Asn | missense_variant | 3/17 | NM_018122.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000675 AC: 1AN: 148096Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460590Hom.: 0 Cov.: 36 AF XY: 0.00000413 AC XY: 3AN XY: 726660
GnomAD4 genome AF: 0.00000675 AC: 1AN: 148096Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 71828
ClinVar
Submissions by phenotype
Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome Pathogenic:1Other:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 17, 2016 | - - |
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at