Variant chr2-135985568-A-G 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.-100T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00771 in 1,589,584 control chromosomes in the GnomAD database, including 257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 100 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 157 hom. )

Consequence

DARS1
NM_001349.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.729

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:40170): (DARS1 antisense RNA 1)

DARS1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 2-135985568-A-G is Benign according to our data. Variant chr2-135985568-A-G is described in ClinVar as [Benign]. Clinvar id is 1251606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
DARS1	NM_001349.4 linkuse as main transcript	c.-100T>C	5_prime_UTR_variant	1/16	ENST00000264161.9	NP_001340.2
DARS1-AS1	NR_110199.1 linkuse as main transcript	n.341+52A>G	intron_variant, non_coding_transcript_variant
DARS1	NM_001293312.1 linkuse as main transcript	c.-342T>C	5_prime_UTR_variant	1/15		NP_001280241.1
DARS1-AS1	NR_110200.1 linkuse as main transcript	n.341+52A>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DARS1	ENST00000264161.9 linkuse as main transcript	c.-100T>C		5_prime_UTR_variant	1/16	1	NM_001349.4	ENSP00000264161	P1	P14868-1
DARS1-AS1	ENST00000692958.1 linkuse as main transcript	n.393+52A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3359

AN:

151724

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00853

Gnomad SAS

AF:

0.0285

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00318

Gnomad OTH

AF:

0.0192

GnomAD3 exomes

AF:

0.0112

AC:

2270

AN:

202298

Hom.:

AF XY:

0.0115

AC XY:

1258

AN XY:

109476

show subpopulations

Gnomad AFR exome

AF:

0.0677

Gnomad AMR exome

AF:

0.00549

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.00611

Gnomad SAS exome

AF:

0.0245

Gnomad FIN exome

AF:

0.00151

Gnomad NFE exome

AF:

0.00346

Gnomad OTH exome

AF:

0.0122

GnomAD4 exome

AF:

0.00616

AC:

8853

AN:

1437746

Hom.:

157

Cov.:

AF XY:

0.00658

AC XY:

4692

AN XY:

712934

show subpopulations

Gnomad4 AFR exome

AF:

0.0687

Gnomad4 AMR exome

AF:

0.00595

Gnomad4 ASJ exome

AF:

0.0187

Gnomad4 EAS exome

AF:

0.0155

Gnomad4 SAS exome

AF:

0.0238

Gnomad4 FIN exome

AF:

0.00140

Gnomad4 NFE exome

AF:

0.00222

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.0224

AC:

3401

AN:

151838

Hom.:

100

Cov.:

AF XY:

0.0230

AC XY:

1706

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.0662

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.00855

Gnomad4 SAS

AF:

0.0286

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00318

Gnomad4 OTH

AF:

0.0190

Alfa

AF:

0.0128

Hom.:

Bravo

AF:

0.0246

Asia WGS

AF:

0.0310

AC:

108

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	clinical testing	GeneDx	Jun 24, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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