rs6752967

Variant names:

• chr2-135985568-A-G
• rs6752967
• NM_001349.4:c.-100T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-135985568-A-G
• chr2-135985568-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.729
• Publications: 3 publications found

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-AS1 (HGNC:40170): (DARS1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DARS1	NM_001349.4	MANE Select	c.-100T>C		5_prime_UTR	Exon 1 of 16	NP_001340.2
	DARS1	NM_001293312.1		c.-342T>C		5_prime_UTR	Exon 1 of 15	NP_001280241.1	P14868-2
	DARS1-AS1	NR_110199.1		n.341+52A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DARS1	ENST00000264161.9	TSL:1 MANE Select	c.-100T>C		5_prime_UTR	Exon 1 of 16	ENSP00000264161.4	P14868-1
	DARS1	ENST00000952144.1		c.-100T>C		5_prime_UTR	Exon 1 of 16	ENSP00000622203.1
	DARS1	ENST00000952145.1		c.-100T>C		5_prime_UTR	Exon 1 of 16	ENSP00000622204.1

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3359 AN: 151724 Hom.: 93 Cov.: 32

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

GnomAD2 exomes AF: 0.0112 AC: 2270 AN: 202298 AF XY: 0.0115

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 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.: 30 AF XY: 0.00658 AC XY: 4692 AN XY: 712934

African (AFR) AF: 0.0687 AC: 2280 AN: 33180

American (AMR) AF: 0.00595 AC: 238 AN: 39976

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 476 AN: 25474

East Asian (EAS) AF: 0.0155 AC: 601 AN: 38846

South Asian (SAS) AF: 0.0238 AC: 1982 AN: 83298

European-Finnish (FIN) AF: 0.00140 AC: 72 AN: 51538

Middle Eastern (MID) AF: 0.0155 AC: 89 AN: 5728

European-Non Finnish (NFE) AF: 0.00222 AC: 2446 AN: 1100224

Other (OTH) AF: 0.0112 AC: 669 AN: 59482

GnomAD4 genome AF: 0.0224 AC: 3401 AN: 151838 Hom.: 100 Cov.: 32 AF XY: 0.0230 AC XY: 1706 AN XY: 74238

African (AFR) AF: 0.0662 AC: 2738 AN: 41376

American (AMR) AF: 0.0114 AC: 174 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3470

East Asian (EAS) AF: 0.00855 AC: 44 AN: 5144

South Asian (SAS) AF: 0.0286 AC: 137 AN: 4798

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10570

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00318 AC: 216 AN: 67898

Other (OTH) AF: 0.0190 AC: 40 AN: 2108

Alfa AF: 0.0134 Hom.: 19

Bravo AF: 0.0246

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.73
PromoterAI		0.067	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6752967; hg19: chr2-136743138;