Variant 2-135985369-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001349.4(DARS1):c.66+34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 1,609,920 control chromosomes in the GnomAD database, including 2,003 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 378 hom., cov: 32)

Exomes 𝑓: 0.024 ( 1625 hom. )

Consequence

DARS1
NM_001349.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.222

Variant links:

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 links:

DARS1-AS1 (HGNC:):

DARS1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 2-135985369-T-C is Benign according to our data. Variant chr2-135985369-T-C is described in ClinVar as [Benign]. Clinvar id is 1258838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
DARS1	NM_001349.4 linkuse as main transcript	c.66+34A>G	intron_variant		ENST00000264161.9	NP_001340.2	P14868-1A0A140VJW5
DARS1	NM_001293312.1 linkuse as main transcript	c.-177+34A>G	intron_variant			NP_001280241.1	P14868-2
DARS1-AS1	NR_110199.1 linkuse as main transcript	n.194T>C	non_coding_transcript_exon_variant	1/4
DARS1-AS1	NR_110200.1 linkuse as main transcript	n.194T>C	non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DARS1	ENST00000264161.9 linkuse as main transcript	c.66+34A>G		intron_variant		1	NM_001349.4	ENSP00000264161.4		P14868-1

Frequencies

GnomAD3 genomes

AF:

0.0500

AC:

7612

AN:

152174

Hom.:

380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0815

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.0894

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.00882

Gnomad OTH

AF:

0.0526

GnomAD3 exomes

AF:

0.0486

AC:

11874

AN:

244276

Hom.:

604

AF XY:

0.0496

AC XY:

6574

AN XY:

132536

show subpopulations

Gnomad AFR exome

AF:

0.0999

Gnomad AMR exome

AF:

0.0872

Gnomad ASJ exome

AF:

0.0233

Gnomad EAS exome

AF:

0.0737

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.00931

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.0363

GnomAD4 exome

AF:

0.0238

AC:

34753

AN:

1457630

Hom.:

1625

Cov.:

AF XY:

0.0267

AC XY:

19331

AN XY:

724882

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.0866

Gnomad4 ASJ exome

AF:

0.0224

Gnomad4 EAS exome

AF:

0.0993

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.00928

Gnomad4 NFE exome

AF:

0.00777

Gnomad4 OTH exome

AF:

0.0334

GnomAD4 genome

AF:

0.0499

AC:

7602

AN:

152290

Hom.:

378

Cov.:

AF XY:

0.0532

AC XY:

3962

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.0812

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.0898

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.0103

Gnomad4 NFE

AF:

0.00884

Gnomad4 OTH

AF:

0.0521

Alfa

AF:

0.0251

Hom.:

Bravo

AF:

0.0536

Asia WGS

AF:

0.132

AC:

458

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 22, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.7

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over