rs192822

Variant names:

• chr2-135924704-A-C
• rs192822
• NM_001349.4:c.565-206T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-135924704-A-C
• chr2-135924704-A-G
• chr2-135924704-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001349.4(DARS1):​c.565-206T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DARS1 NM_001349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DARS1	NM_001349.4	c.565-206T>G		intron_variant	Intron 7 of 15	ENST00000264161.9	NP_001340.2
DARS1	NM_001293312.1	c.265-206T>G		intron_variant	Intron 6 of 14		NP_001280241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DARS1	ENST00000264161.9	c.565-206T>G		intron_variant	Intron 7 of 15	1	NM_001349.4	ENSP00000264161.4
DARS1	ENST00000441323.5	c.466-206T>G		intron_variant	Intron 7 of 7	3		ENSP00000389867.1
DARS1	ENST00000456565.5	c.466-206T>G		intron_variant	Intron 7 of 7	3		ENSP00000397616.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.15

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

Other links and lift over

dbSNP: rs192822; hg19: chr2-136682274;