1-173828312-T-TGGG

Variant names:

• chr1-173828312-T-TGGG
• NM_018122.5:c.228-21_228-20insGGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018122.5(DARS2):​c.228-21_228-20insGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 1,401,806 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: DARS2 NM_018122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DARS2	NM_018122.5	c.228-21_228-20insGGG		intron_variant	Intron 2 of 16	ENST00000649689.2	NP_060592.2
DARS2	NM_001365212.1	c.228-21_228-20insGGG		intron_variant	Intron 2 of 15		NP_001352141.1
DARS2	NM_001365213.2	c.228-21_228-20insGGG		intron_variant	Intron 2 of 13		NP_001352142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DARS2	ENST00000649689.2	c.228-21_228-20insGGG		intron_variant	Intron 2 of 16		NM_018122.5	ENSP00000497569.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.0000264 AC: 37 AN: 1401806 Hom.: 0 Cov.: 22 AF XY: 0.0000201 AC XY: 14 AN XY: 698210

Gnomad4 AFR exome AF: 0.0000310

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000310

Gnomad4 OTH exome AF: 0.0000347

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-173797450;