2-135985740-G-C

Variant names:

• chr2-135985740-G-C
• rs16832394
• ENST00000441323.5:c.-34+73C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000441323.5(DARS1):​c.-34+73C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DARS1 ENST00000441323.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000441323.5. 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-AS1	NR_110199.1		n.341+224G>C		intron	N/A
	DARS1-AS1	NR_110200.1		n.341+224G>C		intron	N/A
	DARS1	NM_001349.4	MANE Select	c.-272C>G		upstream_gene	N/A	NP_001340.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DARS1	ENST00000441323.5	TSL:3	c.-34+73C>G		intron	N/A	ENSP00000389867.1	C9JLC1
	DARS1	ENST00000456565.5	TSL:3	c.-34+190C>G		intron	N/A	ENSP00000397616.1	C9J7S3
	DARS1	ENST00000449218.5	TSL:3	c.-34+54C>G		intron	N/A	ENSP00000388801.1	C9JQM9

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 646110 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 325966

African (AFR) AF: 0.00 AC: 0 AN: 16236

American (AMR) AF: 0.00 AC: 0 AN: 17654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14176

East Asian (EAS) AF: 0.00 AC: 0 AN: 29662

South Asian (SAS) AF: 0.00 AC: 0 AN: 46588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2254

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 461432

Other (OTH) AF: 0.00 AC: 0 AN: 31616

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.5
DANN	Benign	0.73
PhyloP100		0.31
PromoterAI		0.34	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16832394; hg19: chr2-136743310;