dbSNP rs3734908: RARS2:c.1305+18C>T (chr6-87518806-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020320.5(RARS2):c.1305+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 1,613,090 control chromosomes in the GnomAD database, including 2,130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 389 hom., cov: 31)

Exomes 𝑓: 0.045 ( 1741 hom. )

Consequence

RARS2
NM_020320.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.305

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 6-87518806-G-A is Benign according to our data. Variant chr6-87518806-G-A is described in ClinVar as [Benign]. Clinvar id is 261219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-87518806-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARS2	NM_020320.5 link	c.1305+18C>T		intron_variant	Intron 15 of 19	ENST00000369536.10	NP_064716.2	Q5T160

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARS2	ENST00000369536.10 link	c.1305+18C>T		intron_variant	Intron 15 of 19	1	NM_020320.5	ENSP00000358549.5		Q5T160

Frequencies

GnomAD3 genomes

AF:

0.0636

AC:

9666

AN:

152046

Hom.:

387

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.0528

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.0148

Gnomad SAS

AF:

0.0220

Gnomad FIN

AF:

0.0208

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0479

Gnomad OTH

AF:

0.0606

GnomAD3 exomes

AF:

0.0424

AC:

10671

AN:

251424

Hom.:

292

AF XY:

0.0415

AC XY:

5633

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.0367

Gnomad ASJ exome

AF:

0.0240

Gnomad EAS exome

AF:

0.0180

Gnomad SAS exome

AF:

0.0220

Gnomad FIN exome

AF:

0.0228

Gnomad NFE exome

AF:

0.0482

Gnomad OTH exome

AF:

0.0476

GnomAD4 exome

AF:

0.0447

AC:

65273

AN:

1460926

Hom.:

1741

Cov.:

AF XY:

0.0438

AC XY:

31822

AN XY:

726814

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.0387

Gnomad4 ASJ exome

AF:

0.0236

Gnomad4 EAS exome

AF:

0.0207

Gnomad4 SAS exome

AF:

0.0201

Gnomad4 FIN exome

AF:

0.0230

Gnomad4 NFE exome

AF:

0.0469

Gnomad4 OTH exome

AF:

0.0468

GnomAD4 genome

AF:

0.0636

AC:

9674

AN:

152164

Hom.:

389

Cov.:

AF XY:

0.0612

AC XY:

4551

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.0526

Gnomad4 ASJ

AF:

0.0268

Gnomad4 EAS

AF:

0.0151

Gnomad4 SAS

AF:

0.0220

Gnomad4 FIN

AF:

0.0208

Gnomad4 NFE

AF:

0.0479

Gnomad4 OTH

AF:

0.0600

Alfa

AF:

0.0521

Hom.:

Bravo

AF:

0.0696

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pontocerebellar hypoplasia type 6

Benign:1

Jul 10, 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

-0.81

CADD

Benign

2.3

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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