Genetic Variant AARS2:c.*1359A>G (chr6-44299188-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_020745.4(AARS2):c.*1359A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 151,906 control chromosomes in the GnomAD database, including 60,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.89 ( 60931 hom., cov: 29)

Consequence

AARS2
NM_020745.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.23

Publications

4 publications found

Variant links:

Genes affected

AARS2 (HGNC:21022): (alanyl-tRNA synthetase 2, mitochondrial) The protein encoded by this gene belongs to the class-II aminoacyl-tRNA synthetase family. Aminoacyl-tRNA synthetases play critical roles in mRNA translation by charging tRNAs with their cognate amino acids. The encoded protein is a mitochondrial enzyme that specifically aminoacylates alanyl-tRNA. Mutations in this gene are a cause of combined oxidative phosphorylation deficiency 8. [provided by RefSeq, Dec 2011]

AARS2 links:

ENSG00000272442 (HGNC:):

ENSG00000272442 links:

TMEM151B (HGNC:21315): (transmembrane protein 151B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM151B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 6-44299188-T-C is Benign according to our data. Variant chr6-44299188-T-C is described in ClinVar as Benign. ClinVar VariationId is 357032.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020745.4. 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
	AARS2	NM_020745.4	MANE Select	c.*1359A>G		3_prime_UTR	Exon 22 of 22	NP_065796.2	Q5JTZ9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AARS2	ENST00000244571.5	TSL:1 MANE Select	c.*1359A>G	3_prime_UTR	Exon 22 of 22	ENSP00000244571.4	Q5JTZ9
ENSG00000272442	ENST00000505802.1	TSL:2	n.313-7755T>C	intron	N/A	ENSP00000424257.1	H0Y9J4
AARS2	ENST00000932746.1		c.*1359A>G	3_prime_UTR	Exon 21 of 21	ENSP00000602805.1

Frequencies

GnomAD3 genomes

AF:

0.886

AC:

134489

AN:

151788

Hom.:

60894

Cov.:

show subpopulations

Gnomad AFR

AF:

0.676

Gnomad AMI

AF:

0.988

Gnomad AMR

AF:

0.932

Gnomad ASJ

AF:

0.923

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.961

Gnomad FIN

AF:

0.995

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.969

Gnomad OTH

AF:

0.898

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

GnomAD4 genome

AF:

0.886

AC:

134577

AN:

151906

Hom.:

60931

Cov.:

AF XY:

0.888

AC XY:

65911

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.676

AC:

27953

AN:

41344

American (AMR)

AF:

0.932

AC:

14252

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.923

AC:

3203

AN:

3470

East Asian (EAS)

AF:

0.998

AC:

5089

AN:

5098

South Asian (SAS)

AF:

0.962

AC:

4639

AN:

4824

European-Finnish (FIN)

AF:

0.995

AC:

10504

AN:

10558

Middle Eastern (MID)

AF:

0.833

AC:

245

AN:

294

European-Non Finnish (NFE)

AF:

0.969

AC:

65901

AN:

68002

Other (OTH)

AF:

0.896

AC:

1890

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

630

1260

1891

2521

3151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

886

1772

2658

3544

4430

<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:

0.911

Hom.:

8416

Bravo

AF:

0.871

Asia WGS

AF:

0.938

AC:

3262

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Combined oxidative phosphorylation defect type 8 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.61

(source)

DANN

Benign

0.57

PhyloP100

-1.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over