Variant 2-135985510-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001349.4(DARS1):c.-42C>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 0.00603 in 1,613,704 control chromosomes in the GnomAD database, including 737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 99 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 638 hom. )

Consequence

DARS1
NM_001349.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.17

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 2-135985510-G-C is Benign according to our data. Variant chr2-135985510-G-C is described in ClinVar as [Benign]. Clinvar id is 381868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
DARS1	NM_001349.4 linkuse as main transcript	c.-42C>G	5_prime_UTR_variant	1/16	ENST00000264161.9	NP_001340.2
DARS1-AS1	NR_110199.1 linkuse as main transcript	n.335G>C	non_coding_transcript_exon_variant	1/4
DARS1	NM_001293312.1 linkuse as main transcript	c.-284C>G	5_prime_UTR_variant	1/15		NP_001280241.1
DARS1-AS1	NR_110200.1 linkuse as main transcript	n.335G>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.-42C>G		5_prime_UTR_variant	1/16	1	NM_001349.4	ENSP00000264161	P1	P14868-1
DARS1-AS1	ENST00000692958.1 linkuse as main transcript	n.387G>C		non_coding_transcript_exon_variant	1/4

Frequencies

GnomAD3 genomes

AF:

0.00766

AC:

1165

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.0161

AC:

4016

AN:

249648

Hom.:

351

AF XY:

0.0149

AC XY:

2019

AN XY:

135180

show subpopulations

Gnomad AFR exome

AF:

0.000435

Gnomad AMR exome

AF:

0.000928

Gnomad ASJ exome

AF:

0.00777

Gnomad EAS exome

AF:

0.198

Gnomad SAS exome

AF:

0.00573

Gnomad FIN exome

AF:

0.000563

Gnomad NFE exome

AF:

0.000372

Gnomad OTH exome

AF:

0.00773

GnomAD4 exome

AF:

0.00586

AC:

8558

AN:

1461424

Hom.:

638

Cov.:

AF XY:

0.00584

AC XY:

4243

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000783

Gnomad4 ASJ exome

AF:

0.00846

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.00640

Gnomad4 FIN exome

AF:

0.000450

Gnomad4 NFE exome

AF:

0.000212

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.00765

AC:

1165

AN:

152280

Hom.:

Cov.:

AF XY:

0.00878

AC XY:

654

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.195

Gnomad4 SAS

AF:

0.0112

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00142

Hom.:

Bravo

AF:

0.00947

Asia WGS

AF:

0.0720

AC:

251

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 07, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

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

-0.26

CADD

Benign

DANN

Uncertain

0.99

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

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