1-173827031-A-G

Position:

• chr1-173827031-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018122.5(DARS2):​c.227+245A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0823 in 152,260 control chromosomes in the GnomAD database, including 739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.082 (739 hom., cov: 32)
• Consequence: DARS2 NM_018122.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.20

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-173827031-A-G is Benign according to our data. Variant chr1-173827031-A-G is described in ClinVar as [Benign]. Clinvar id is 683695.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DARS2	NM_018122.5	c.227+245A>G		intron_variant		ENST00000649689.2
DARS2	NM_001365212.1	c.227+245A>G		intron_variant
DARS2	NM_001365213.2	c.227+245A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DARS2	ENST00000649689.2	c.227+245A>G		intron_variant			NM_018122.5	P1

Frequencies

GnomAD3 genomes AF: 0.0824 AC: 12537 AN: 152142 Hom.: 740 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0753

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0794

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0888

Gnomad OTH AF: 0.0899

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0823 AC: 12538 AN: 152260 Hom.: 739 Cov.: 32 AF XY: 0.0829 AC XY: 6172 AN XY: 74450

Gnomad4 AFR AF: 0.0394

Gnomad4 AMR AF: 0.0752

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0794

Gnomad4 NFE AF: 0.0888

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0900 Hom.: 1518

Bravo AF: 0.0803

Asia WGS AF: 0.207 AC: 721 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.055
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2068871; hg19: chr1-173796169;