Variant 2-135985740-G-T 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 ENST00000441323.5(DARS1):c.-34+73C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00876 in 798,368 control chromosomes in the GnomAD database, including 536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 99 hom., cov: 33)

Exomes 𝑓: 0.0090 ( 437 hom. )

Consequence

DARS1
ENST00000441323.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.310

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=-0.67).

BP6

Variant 2-135985740-G-T is Benign according to our data. Variant chr2-135985740-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1202907.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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DARS1-AS1	NR_110199.1 linkuse as main transcript	n.341+224G>T		intron_variant
DARS1-AS1	NR_110200.1 linkuse as main transcript	n.341+224G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
DARS1	ENST00000441323.5 linkuse as main transcript	c.-34+73C>A	intron_variant	3	ENSP00000389867.1	C9JLC1
DARS1	ENST00000456565.5 linkuse as main transcript	c.-34+190C>A	intron_variant	3	ENSP00000397616.1	C9J7S3
DARS1	ENST00000449218.5 linkuse as main transcript	c.-34+54C>A	intron_variant	3	ENSP00000388801.1	C9JQM9

Frequencies

GnomAD3 genomes

AF:

0.00765

AC:

1164

AN:

152206

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:

0.0110

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00669

GnomAD4 exome

AF:

0.00902

AC:

5826

AN:

646044

Hom.:

437

Cov.:

AF XY:

0.00880

AC XY:

2867

AN XY:

325938

show subpopulations

Gnomad4 AFR exome

AF:

0.000123

Gnomad4 AMR exome

AF:

0.000566

Gnomad4 ASJ exome

AF:

0.00804

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.00618

Gnomad4 FIN exome

AF:

0.000453

Gnomad4 NFE exome

AF:

0.000297

Gnomad4 OTH exome

AF:

0.0111

GnomAD4 genome

AF:

0.00764

AC:

1164

AN:

152324

Hom.:

Cov.:

AF XY:

0.00875

AC XY:

652

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000914

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.195

Gnomad4 SAS

AF:

0.0110

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.000621

Hom.:

Bravo

AF:

0.00946

Asia WGS

AF:

0.0720

AC:

251

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.3

DANN

Benign

0.87

Splicing

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