chr2-135985436-C-T

Variant names:

• chr2-135985436-C-T
• rs1288683559
• NM_001349.4:c.33G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001349.4(DARS1):​c.33G>A​(p.Gln11Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DARS1 NM_001349.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.45
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP6: Variant 2-135985436-C-T is Benign according to our data. Variant chr2-135985436-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3706938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.45 with no splicing effect.

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.33G>A	p.Gln11Gln	synonymous	Exon 1 of 16	NP_001340.2
	DARS1	NM_001293312.1		c.-210G>A		5_prime_UTR	Exon 1 of 15	NP_001280241.1	P14868-2
	DARS1-AS1	NR_110199.1		n.261C>T		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DARS1	ENST00000264161.9	TSL:1 MANE Select	c.33G>A	p.Gln11Gln	synonymous	Exon 1 of 16	ENSP00000264161.4	P14868-1
	DARS1	ENST00000952144.1		c.33G>A	p.Gln11Gln	synonymous	Exon 1 of 16	ENSP00000622203.1
	DARS1	ENST00000952145.1		c.33G>A	p.Gln11Gln	synonymous	Exon 1 of 16	ENSP00000622204.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250320 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Benign	0.96
PhyloP100		1.4
PromoterAI		-0.088	Neutral
Mutation Taster		=246/54	polymorphism

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: rs1288683559; hg19: chr2-136743006;