rs2322725

Positions:

• chr2-135919622-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349.4(DARS1):​c.959+831A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,142 control chromosomes in the GnomAD database, including 3,332 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3332 hom., cov: 32)
• Consequence: DARS1 NM_001349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.932

Genes affected

DARS1 (HGNC:2678): (aspartyl-tRNA synthetase 1) This gene encodes a member of a multienzyme complex that functions in mediating the attachment of amino acids to their cognate tRNAs. The encoded protein ligates L-aspartate to tRNA(Asp). Mutations in this gene have been found in patients showing hypomyelination with brainstem and spinal cord involvement and leg spasticity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DARS1	NM_001349.4	c.959+831A>G		intron_variant		ENST00000264161.9	NP_001340.2
DARS1	NM_001293312.1	c.659+831A>G		intron_variant			NP_001280241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DARS1	ENST00000264161.9	c.959+831A>G		intron_variant		1	NM_001349.4	ENSP00000264161	P1
DARS1	ENST00000422708.3	c.101+831A>G		intron_variant		2		ENSP00000387508

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28799 AN: 152024 Hom.: 3328 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.189 AC: 28820 AN: 152142 Hom.: 3332 Cov.: 32 AF XY: 0.197 AC XY: 14621 AN XY: 74382

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.217

Alfa AF: 0.154 Hom.: 463

Bravo AF: 0.203

Asia WGS AF: 0.285 AC: 986 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	14
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2322725; hg19: chr2-136677192;