2-135957754-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.320+3642A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,032 control chromosomes in the GnomAD database, including 6,026 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 0.26 (6026 hom., cov: 31)
• Consequence: DARS1 NM_001349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DARS1	NM_001349.4	c.320+3642A>G		intron_variant		ENST00000264161.9
DARS1	NM_001293312.1	c.20+3642A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DARS1	ENST00000264161.9	c.320+3642A>G		intron_variant		1	NM_001349.4	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39157 AN: 151914 Hom.: 5998 Cov.: 31

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.258 AC: 39238 AN: 152032 Hom.: 6026 Cov.: 31 AF XY: 0.261 AC XY: 19389 AN XY: 74328

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.313

Alfa AF: 0.143 Hom.: 376

Bravo AF: 0.272

Asia WGS AF: 0.328 AC: 1140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.1
Dann	Benign	0.67

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: rs309142; hg19: chr2-136715324;