2-135985447-G-GGCTGGC

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM4BP6BS1

The NM_001349.4(DARS1):​c.16_21dupGCCAGC​(p.Ser7_Arg8insAlaSer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00032 in 1,613,926 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00029 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

DARS1
NM_001349.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 2.18
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-AS1 (HGNC:40170): (DARS1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM4
Nonframeshift variant in NON repetitive region in NM_001349.4.
BP6
Variant 2-135985447-G-GGCTGGC is Benign according to our data. Variant chr2-135985447-G-GGCTGGC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 808803.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000289 (44/152334) while in subpopulation SAS AF= 0.00394 (19/4826). AF 95% confidence interval is 0.00258. There are 1 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DARS1NM_001349.4 linkc.16_21dupGCCAGC p.Ser7_Arg8insAlaSer conservative_inframe_insertion Exon 1 of 16 ENST00000264161.9 NP_001340.2 P14868-1A0A140VJW5
DARS1NM_001293312.1 linkc.-227_-222dupGCCAGC 5_prime_UTR_variant Exon 1 of 15 NP_001280241.1 P14868-2
DARS1-AS1NR_110199.1 linkn.284_289dupCGCTGG non_coding_transcript_exon_variant Exon 1 of 4
DARS1-AS1NR_110200.1 linkn.284_289dupCGCTGG non_coding_transcript_exon_variant Exon 1 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DARS1ENST00000264161.9 linkc.16_21dupGCCAGC p.Ser7_Arg8insAlaSer conservative_inframe_insertion Exon 1 of 16 1 NM_001349.4 ENSP00000264161.4 P14868-1

Frequencies

GnomAD3 genomes
AF:
0.000289
AC:
44
AN:
152216
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00393
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000520
AC:
130
AN:
250022
Hom.:
1
AF XY:
0.000679
AC XY:
92
AN XY:
135398
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000222
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000324
AC:
473
AN:
1461592
Hom.:
1
Cov.:
31
AF XY:
0.000430
AC XY:
313
AN XY:
727132
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00381
Gnomad4 FIN exome
AF:
0.0000751
Gnomad4 NFE exome
AF:
0.0000935
Gnomad4 OTH exome
AF:
0.000398
GnomAD4 genome
AF:
0.000289
AC:
44
AN:
152334
Hom.:
1
Cov.:
32
AF XY:
0.000322
AC XY:
24
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00394
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.000217
Hom.:
0
Bravo
AF:
0.000159
EpiCase
AF:
0.000382
EpiControl
AF:
0.000356

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJun 01, 2016- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 14, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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.

Other links and lift over

dbSNP: rs551090724; hg19: chr2-136743017; API