chr3-45491732-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015340.4(LARS2):c.1455G>A(p.Ala485Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 1,614,084 control chromosomes in the GnomAD database, including 697,058 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 52827 hom., cov: 32)

Exomes 𝑓: 0.93 ( 644231 hom. )

Consequence

LARS2
NM_015340.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.83

Publications

24 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 -21 ACMG points.

BP4

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

BP6

Variant 3-45491732-G-A is Benign according to our data. Variant chr3-45491732-G-A is described in ClinVar as Benign. ClinVar VariationId is 226693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.83 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LARS2	NM_015340.4 link	c.1455G>A	p.Ala485Ala	synonymous_variant	Exon 13 of 22	ENST00000645846.2	NP_056155.1	Q15031

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LARS2	ENST00000645846.2 link	c.1455G>A	p.Ala485Ala	synonymous_variant	Exon 13 of 22		NM_015340.4	ENSP00000495093.1		Q15031

Frequencies

GnomAD3 genomes

AF:

0.799

AC:

121611

AN:

152118

Hom.:

52811

Cov.:

show subpopulations

Gnomad AFR

AF:

0.422

Gnomad AMI

AF:

0.986

Gnomad AMR

AF:

0.905

Gnomad ASJ

AF:

0.889

Gnomad EAS

AF:

0.976

Gnomad SAS

AF:

0.920

Gnomad FIN

AF:

0.976

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.948

Gnomad OTH

AF:

0.826

GnomAD2 exomes

AF:

0.912

AC:

229280

AN:

251372

AF XY:

0.921

show subpopulations

Gnomad AFR exome

AF:

0.413

Gnomad AMR exome

AF:

0.946

Gnomad ASJ exome

AF:

0.885

Gnomad EAS exome

AF:

0.978

Gnomad FIN exome

AF:

0.973

Gnomad NFE exome

AF:

0.948

Gnomad OTH exome

AF:

0.918

GnomAD4 exome

AF:

0.935

AC:

1366633

AN:

1461848

Hom.:

644231

Cov.:

AF XY:

0.936

AC XY:

680828

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.403

AC:

13477

AN:

33478

American (AMR)

AF:

0.940

AC:

42048

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.882

AC:

23048

AN:

26134

East Asian (EAS)

AF:

0.978

AC:

38807

AN:

39700

South Asian (SAS)

AF:

0.929

AC:

80148

AN:

86258

European-Finnish (FIN)

AF:

0.971

AC:

51867

AN:

53420

Middle Eastern (MID)

AF:

0.885

AC:

5103

AN:

5768

European-Non Finnish (NFE)

AF:

0.951

AC:

1057310

AN:

1111974

Other (OTH)

AF:

0.908

AC:

54825

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

4559

9118

13678

18237

22796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21514

43028

64542

86056

107570

<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:

0.799

AC:

121660

AN:

152236

Hom.:

52827

Cov.:

AF XY:

0.805

AC XY:

59958

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.421

AC:

17487

AN:

41496

American (AMR)

AF:

0.905

AC:

13852

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.889

AC:

3088

AN:

3472

East Asian (EAS)

AF:

0.976

AC:

5058

AN:

5184

South Asian (SAS)

AF:

0.920

AC:

4434

AN:

4820

European-Finnish (FIN)

AF:

0.976

AC:

10368

AN:

10626

Middle Eastern (MID)

AF:

0.864

AC:

254

AN:

294

European-Non Finnish (NFE)

AF:

0.948

AC:

64478

AN:

68018

Other (OTH)

AF:

0.828

AC:

1742

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

834

1669

2503

3338

4172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<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:

0.867

Hom.:

27464

Bravo

AF:

0.775

Asia WGS

AF:

0.915

AC:

3180

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ala485Ala in exon 13 of LARS2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 44.0% (1938/4406) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2128361). -

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 16, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

0.037

(source)

DANN

Benign

0.65

PhyloP100

-3.8

Mutation Taster

=99/1

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