rs2306522

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015340.4(LARS2):c.1760+12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,539,344 control chromosomes in the GnomAD database, including 307,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 24080 hom., cov: 33)

Exomes 𝑓: 0.63 ( 283206 hom. )

Consequence

LARS2
NM_015340.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.62

Publications

14 publications found

Variant links:

Genes affected

LARS2 (HGNC:17095): (leucyl-tRNA synthetase 2, mitochondrial) This gene encodes a class 1 aminoacyl-tRNA synthetase, mitochondrial leucyl-tRNA synthetase. Each of the twenty aminoacyl-tRNA synthetases catalyzes the aminoacylation of a specific tRNA or tRNA isoaccepting family with the cognate amino acid. [provided by RefSeq, Jul 2008]

LARS2 links:

LARS2-AS1 (HGNC:40796): (LARS2 antisense RNA 1)

LARS2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-45500591-T-C is Benign according to our data. Variant chr3-45500591-T-C is described in ClinVar as Benign. ClinVar VariationId is 226697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LARS2	NM_015340.4 link	c.1760+12T>C		intron_variant	Intron 15 of 21	ENST00000645846.2	NP_056155.1	Q15031

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LARS2	ENST00000645846.2 link	c.1760+12T>C		intron_variant	Intron 15 of 21		NM_015340.4	ENSP00000495093.1		Q15031

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

78278

AN:

152032

Hom.:

24071

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.795

Gnomad AMR

AF:

0.606

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.780

Gnomad SAS

AF:

0.557

Gnomad FIN

AF:

0.778

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.637

Gnomad OTH

AF:

0.504

GnomAD2 exomes

AF:

0.625

AC:

119615

AN:

191354

AF XY:

0.624

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.748

Gnomad ASJ exome

AF:

0.535

Gnomad EAS exome

AF:

0.784

Gnomad FIN exome

AF:

0.762

Gnomad NFE exome

AF:

0.630

Gnomad OTH exome

AF:

0.617

GnomAD4 exome

AF:

0.633

AC:

877652

AN:

1387194

Hom.:

283206

Cov.:

AF XY:

0.631

AC XY:

434267

AN XY:

688272

show subpopulations

African (AFR)

AF:

0.145

AC:

4081

AN:

28226

American (AMR)

AF:

0.720

AC:

19570

AN:

27172

Ashkenazi Jewish (ASJ)

AF:

0.523

AC:

12506

AN:

23910

East Asian (EAS)

AF:

0.773

AC:

27612

AN:

35722

South Asian (SAS)

AF:

0.566

AC:

42150

AN:

74504

European-Finnish (FIN)

AF:

0.749

AC:

39429

AN:

52666

Middle Eastern (MID)

AF:

0.473

AC:

2628

AN:

5558

European-Non Finnish (NFE)

AF:

0.642

AC:

695117

AN:

1082142

Other (OTH)

AF:

0.603

AC:

34559

AN:

57294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

14388

28776

43163

57551

71939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18460

36920

55380

73840

92300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.515

AC:

78297

AN:

152150

Hom.:

24080

Cov.:

AF XY:

0.524

AC XY:

38987

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.170

AC:

7064

AN:

41510

American (AMR)

AF:

0.607

AC:

9266

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

1777

AN:

3470

East Asian (EAS)

AF:

0.780

AC:

4038

AN:

5178

South Asian (SAS)

AF:

0.557

AC:

2685

AN:

4822

European-Finnish (FIN)

AF:

0.778

AC:

8243

AN:

10592

Middle Eastern (MID)

AF:

0.466

AC:

136

AN:

292

European-Non Finnish (NFE)

AF:

0.637

AC:

43303

AN:

67994

Other (OTH)

AF:

0.502

AC:

1060

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1598

3196

4794

6392

7990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.559

Hom.:

9054

Bravo

AF:

0.488

Asia WGS

AF:

0.657

AC:

2284

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

1760+12T>C in intron 15 of LARS2: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 37.1% (3193/8600) of European American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs2306522). -

Dec 02, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Perrault syndrome 4

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.028

(source)

DANN

Benign

0.58

PhyloP100

-3.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over