2-135953494-C-T

Position:

• chr2-135953494-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.320+7902G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,920 control chromosomes in the GnomAD database, including 5,586 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 0.25 (5586 hom., cov: 32)
• Consequence: DARS1 NM_001349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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]

DARS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DARS1	NM_001349.4	c.320+7902G>A		intron_variant		ENST00000264161.9	NP_001340.2
DARS1	NM_001293312.1	c.20+7902G>A		intron_variant			NP_001280241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DARS1	ENST00000264161.9	c.320+7902G>A		intron_variant		1	NM_001349.4	ENSP00000264161.4

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37481 AN: 151802 Hom.: 5556 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.247 AC: 37565 AN: 151920 Hom.: 5586 Cov.: 32 AF XY: 0.250 AC XY: 18594 AN XY: 74234

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.300

Alfa AF: 0.143 Hom.: 373

Bravo AF: 0.261

Asia WGS AF: 0.314 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.34

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: rs3112496; hg19: chr2-136711064;