Genetic Variant RARS2:c.*110G>A (chr6-87514303-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001350505.2(RARS2):c.1728G>A(p.Glu576Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00094 in 674,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00096 ( 0 hom. )

Consequence

RARS2
NM_001350505.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.132

Variant links:

Genes affected

RARS2 (HGNC:21406): (arginyl-tRNA synthetase 2, mitochondrial) This nuclear gene encodes a protein that localizes to the mitochondria, where it catalyzes the transfer of L-arginine to its cognate tRNA, an important step in translation of mitochondrially-encoded proteins. Defects in this gene are a cause of pontocerebellar hypoplasia type 6 (PCH6). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

RARS2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 6-87514303-C-T is Benign according to our data. Variant chr6-87514303-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3770781.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.132 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARS2	NM_020320.5 link	c.*110G>A		3_prime_UTR_variant	Exon 20 of 20	ENST00000369536.10	NP_064716.2	Q5T160

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARS2	ENST00000369536 link	c.*110G>A		3_prime_UTR_variant	Exon 20 of 20	1	NM_020320.5	ENSP00000358549.5		Q5T160

Frequencies

GnomAD3 genomes

AF:

0.000861

AC:

120

AN:

139326

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000267

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000376

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000960

AC:

514

AN:

535286

Hom.:

AF XY:

0.000904

AC XY:

260

AN XY:

287534

show subpopulations

Gnomad4 AFR exome

AF:

0.0000796

Gnomad4 AMR exome

AF:

0.000221

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000733

Gnomad4 FIN exome

AF:

0.000148

Gnomad4 NFE exome

AF:

0.00138

Gnomad4 OTH exome

AF:

0.000932

GnomAD4 genome

AF:

0.000861

AC:

120

AN:

139424

Hom.:

Cov.:

AF XY:

0.000744

AC XY:

AN XY:

67178

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.000375

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00126

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RARS2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

4.0

DANN

Benign

0.48

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over