Variant rs2532938 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020442.6(VARS2):c.3090+46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,612,636 control chromosomes in the GnomAD database, including 93,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6836 hom., cov: 33)

Exomes 𝑓: 0.34 ( 86675 hom. )

Consequence

VARS2
NM_020442.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.54

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 (BayesDel_noAF=-0.85).

BP6

Variant 6-30926054-G-A is Benign according to our data. Variant chr6-30926054-G-A is described in ClinVar as [Benign]. Clinvar id is 1292282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
VARS2	NM_020442.6 linkuse as main transcript	c.3090+46G>A	intron_variant	ENST00000676266.1	NP_065175.4
VARS2	NM_001167733.3 linkuse as main transcript	c.2670+46G>A	intron_variant		NP_001161205.1
VARS2	NM_001167734.2 linkuse as main transcript	c.3180+46G>A	intron_variant		NP_001161206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VARS2	ENST00000676266.1 linkuse as main transcript	c.3090+46G>A		intron_variant			NM_020442.6	ENSP00000502585	P3	Q5ST30-1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42555

AN:

152038

Hom.:

6839

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.282

GnomAD3 exomes

AF:

0.316

AC:

77861

AN:

246172

Hom.:

13166

AF XY:

0.324

AC XY:

43475

AN XY:

134224

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.381

Gnomad EAS exome

AF:

0.283

Gnomad SAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.335

GnomAD4 exome

AF:

0.339

AC:

495623

AN:

1460480

Hom.:

86675

Cov.:

AF XY:

0.339

AC XY:

246421

AN XY:

726516

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.220

Gnomad4 ASJ exome

AF:

0.375

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.386

Gnomad4 NFE exome

AF:

0.358

Gnomad4 OTH exome

AF:

0.311

GnomAD4 genome

AF:

0.280

AC:

42565

AN:

152156

Hom.:

6836

Cov.:

AF XY:

0.281

AC XY:

20883

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.401

Gnomad4 EAS

AF:

0.253

Gnomad4 SAS

AF:

0.263

Gnomad4 FIN

AF:

0.392

Gnomad4 NFE

AF:

0.362

Gnomad4 OTH

AF:

0.279

Alfa

AF:

0.345

Hom.:

6272

Bravo

AF:

0.263

Asia WGS

AF:

0.207

AC:

725

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 47. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.059

DANN

Benign

0.54

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