chr6-30915026-G-A

Position:

chr6-30915026-G-A

Variant summary

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

The NM_020442.6(VARS2):c.190G>A(p.Gly64Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 1,613,386 control chromosomes in the GnomAD database, including 2,013 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.065 ( 506 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1507 hom. )

Consequence

VARS2
NM_020442.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.714

Variant links:

Genes affected

VARS2 (HGNC:21642): (valyl-tRNA synthetase 2, mitochondrial) This gene encodes a mitochondrial aminoacyl-tRNA synthetase, which catalyzes the attachment of valine to tRNA(Val) for mitochondrial translation. Mutations in this gene cause combined oxidative phosphorylation deficiency-20, and are also associated with early-onset mitochondrial encephalopathies. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2014]

VARS2 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 (MetaRNN=0.0015696287).

BP6

Variant 6-30915026-G-A is Benign according to our data. Variant chr6-30915026-G-A is described in ClinVar as [Benign]. Clinvar id is 380189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-30915026-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
VARS2	NM_020442.6 linkuse as main transcript	c.190G>A	p.Gly64Arg	missense_variant	2/30	ENST00000676266.1
VARS2	NM_001167734.2 linkuse as main transcript	c.280G>A	p.Gly94Arg	missense_variant	2/30
VARS2	NM_001167733.3 linkuse as main transcript	c.-219-130G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VARS2	ENST00000676266.1 linkuse as main transcript	c.190G>A	p.Gly64Arg	missense_variant	2/30		NM_020442.6	P3	Q5ST30-1

Frequencies

GnomAD3 genomes

AF:

0.0646

AC:

9829

AN:

152124

Hom.:

504

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0891

Gnomad ASJ

AF:

0.0913

Gnomad EAS

AF:

0.0631

Gnomad SAS

AF:

0.0319

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0319

Gnomad OTH

AF:

0.0660

GnomAD3 exomes

AF:

0.0506

AC:

12562

AN:

248130

Hom.:

501

AF XY:

0.0467

AC XY:

6296

AN XY:

134852

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.0992

Gnomad ASJ exome

AF:

0.0930

Gnomad EAS exome

AF:

0.0627

Gnomad SAS exome

AF:

0.0339

Gnomad FIN exome

AF:

0.00925

Gnomad NFE exome

AF:

0.0325

Gnomad OTH exome

AF:

0.0497

GnomAD4 exome

AF:

0.0365

AC:

53278

AN:

1461144

Hom.:

1507

Cov.:

AF XY:

0.0362

AC XY:

26295

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.0966

Gnomad4 ASJ exome

AF:

0.0895

Gnomad4 EAS exome

AF:

0.0616

Gnomad4 SAS exome

AF:

0.0335

Gnomad4 FIN exome

AF:

0.00981

Gnomad4 NFE exome

AF:

0.0297

Gnomad4 OTH exome

AF:

0.0490

GnomAD4 genome

AF:

0.0646

AC:

9842

AN:

152242

Hom.:

506

Cov.:

AF XY:

0.0638

AC XY:

4751

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.0891

Gnomad4 ASJ

AF:

0.0913

Gnomad4 EAS

AF:

0.0632

Gnomad4 SAS

AF:

0.0317

Gnomad4 FIN

AF:

0.0107

Gnomad4 NFE

AF:

0.0319

Gnomad4 OTH

AF:

0.0649

Alfa

AF:

0.0422

Hom.:

353

Bravo

AF:

0.0748

TwinsUK

AF:

0.0294

AC:

109

ALSPAC

AF:

0.0319

AC:

123

ESP6500AA

AF:

0.117

AC:

354

ESP6500EA

AF:

0.0353

AC:

191

ExAC

AF:

0.0484

AC:

5866

Asia WGS

AF:

0.0560

AC:

194

AN:

3478

EpiCase

AF:

0.0366

EpiControl

AF:

0.0371

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 29, 2016	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 17, 2015

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.62

DANN

Benign

0.80

DEOGEN2

Benign

0.0034

T;T;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.31

T;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.010

Sift

Benign

0.45

T;T;T;T

Sift4G

Benign

0.45

T;T;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.026

MutPred

0.12

Gain of MoRF binding (P = 0.0157);Gain of MoRF binding (P = 0.0157);.;Gain of MoRF binding (P = 0.0157);

MPC

0.54

ClinPred

0.0061

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.047

gMVP

0.18

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

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