chr2-135927658-C-T

Variant names:

• chr2-135927658-C-T
• rs309160
• NM_001349.4:c.565-3160G>A

Variant summary

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

The NM_001349.4(DARS1):​c.565-3160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,832 control chromosomes in the GnomAD database, including 24,441 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 0.51 (24441 hom., cov: 32)
• Consequence: DARS1 NM_001349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161

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]

LOC124906078 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DARS1	NM_001349.4	c.565-3160G>A		intron_variant	Intron 7 of 15	ENST00000264161.9	NP_001340.2
DARS1	NM_001293312.1	c.265-3160G>A		intron_variant	Intron 6 of 14		NP_001280241.1
LOC124906078	XR_007087246.1	n.2298-1831G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DARS1	ENST00000264161.9	c.565-3160G>A		intron_variant	Intron 7 of 15	1	NM_001349.4	ENSP00000264161.4
DARS1	ENST00000441323.5	c.466-3160G>A		intron_variant	Intron 7 of 7	3		ENSP00000389867.1
DARS1	ENST00000456565.5	c.466-3160G>A		intron_variant	Intron 7 of 7	3		ENSP00000397616.1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77569 AN: 151714 Hom.: 24382 Cov.: 32

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.512 AC: 77685 AN: 151832 Hom.: 24441 Cov.: 32 AF XY: 0.520 AC XY: 38601 AN XY: 74180

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.576

Alfa AF: 0.381 Hom.: 17326

Bravo AF: 0.546

Asia WGS AF: 0.633 AC: 2192 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.3
DANN	Benign	0.70

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: rs309160; hg19: chr2-136685228;