rs2164331

Positions:

• chr2-135910326-C-T

Variant summary

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

The NM_001349.4(DARS1):​c.1414+813G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,032 control chromosomes in the GnomAD database, including 3,038 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 0.18 (3038 hom., cov: 32)
• Consequence: DARS1 NM_001349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DARS1	NM_001349.4	c.1414+813G>A		intron_variant		ENST00000264161.9
DARS1	NM_001293312.1	c.1114+813G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DARS1	ENST00000264161.9	c.1414+813G>A		intron_variant		1	NM_001349.4	P1
DARS1	ENST00000422708.3	c.475+813G>A		intron_variant		2
DARS1	ENST00000478212.5	n.308+813G>A		intron_variant, non_coding_transcript_variant		2
DARS1	ENST00000489964.5	n.663+813G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27131 AN: 151914 Hom.: 3034 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.179 AC: 27151 AN: 152032 Hom.: 3038 Cov.: 32 AF XY: 0.186 AC XY: 13823 AN XY: 74318

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.203

Alfa AF: 0.140 Hom.: 405

Bravo AF: 0.192

Asia WGS AF: 0.278 AC: 963 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.43

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: rs2164331; hg19: chr2-136667896;