Variant 2-135985573-G-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.-105C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,584,088 control chromosomes in the GnomAD database, including 28,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4406 hom., cov: 32)

Exomes 𝑓: 0.16 ( 24430 hom. )

Consequence

DARS1
NM_001349.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.22

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:

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=-0.72).

BP6

Variant 2-135985573-G-C is Benign according to our data. Variant chr2-135985573-G-C is described in ClinVar as [Benign]. Clinvar id is 1181810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 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.-105C>G	5_prime_UTR_variant	1/16	ENST00000264161.9	NP_001340.2	P14868-1A0A140VJW5
DARS1	NM_001293312.1 linkuse as main transcript	c.-347C>G	5_prime_UTR_variant	1/15		NP_001280241.1	P14868-2
DARS1-AS1	NR_110199.1 linkuse as main transcript	n.341+57G>C	intron_variant
DARS1-AS1	NR_110200.1 linkuse as main transcript	n.341+57G>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DARS1	ENST00000264161.9 linkuse as main transcript	c.-105C>G		5_prime_UTR_variant	1/16	1	NM_001349.4	ENSP00000264161.4		P14868-1

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33907

AN:

152006

Hom.:

4384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.426

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.395

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.274

GnomAD3 exomes

AF:

0.226

AC:

44724

AN:

197716

Hom.:

6176

AF XY:

0.230

AC XY:

24653

AN XY:

106956

show subpopulations

Gnomad AFR exome

AF:

0.294

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.448

Gnomad EAS exome

AF:

0.414

Gnomad SAS exome

AF:

0.290

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.252

GnomAD4 exome

AF:

0.161

AC:

230880

AN:

1431964

Hom.:

24430

Cov.:

AF XY:

0.167

AC XY:

118622

AN XY:

709284

show subpopulations

Gnomad4 AFR exome

AF:

0.314

Gnomad4 AMR exome

AF:

0.198

Gnomad4 ASJ exome

AF:

0.443

Gnomad4 EAS exome

AF:

0.352

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.206

GnomAD4 genome

AF:

0.223

AC:

33978

AN:

152124

Hom.:

4406

Cov.:

AF XY:

0.228

AC XY:

16941

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.293

Gnomad4 AMR

AF:

0.246

Gnomad4 ASJ

AF:

0.426

Gnomad4 EAS

AF:

0.396

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.160

Gnomad4 OTH

AF:

0.280

Alfa

AF:

0.231

Hom.:

942

Bravo

AF:

0.234

Asia WGS

AF:

0.306

AC:

1066

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	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.9

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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