2-135950412-T-C

Variant names:

• chr2-135950412-T-C
• rs6754311
• NM_001349.4:c.321-6932A>G

Variant summary

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

The NM_001349.4(DARS1):​c.321-6932A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 152,136 control chromosomes in the GnomAD database, including 33,082 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 0.60 (33082 hom., cov: 32)
• Consequence: DARS1 NM_001349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450

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 (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DARS1	NM_001349.4	c.321-6932A>G		intron_variant	Intron 4 of 15	ENST00000264161.9	NP_001340.2
DARS1	NM_001293312.1	c.21-6932A>G		intron_variant	Intron 3 of 14		NP_001280241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DARS1	ENST00000264161.9	c.321-6932A>G		intron_variant	Intron 4 of 15	1	NM_001349.4	ENSP00000264161.4

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91451 AN: 152018 Hom.: 33015 Cov.: 32

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.933

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.602 AC: 91582 AN: 152136 Hom.: 33082 Cov.: 32 AF XY: 0.618 AC XY: 45936 AN XY: 74374

Gnomad4 AFR AF: 0.880

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.704

Alfa AF: 0.442 Hom.: 4792

Bravo AF: 0.639

Asia WGS AF: 0.923 AC: 3209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.64

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: rs6754311; hg19: chr2-136707982;