Variant 6-30914500-C-T 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 ENST00000321897.9(VARS2):c.-337C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,329,760 control chromosomes in the GnomAD database, including 77,967 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6828 hom., cov: 32)

Exomes 𝑓: 0.34 ( 71139 hom. )

Consequence

VARS2
ENST00000321897.9 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0870

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:

ENSG00000288473 (HGNC:):

ENSG00000288473 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 6-30914500-C-T is Benign according to our data. Variant chr6-30914500-C-T is described in ClinVar as [Benign]. Clinvar id is 1271839.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	UniProt
VARS2	NM_020442.6 linkuse as main transcript	c.-28+156C>T	intron_variant	ENST00000676266.1	NP_065175.4	Q5ST30-1B4E0K6B4DG77
VARS2	NM_001167734.2 linkuse as main transcript	c.58+31C>T	intron_variant		NP_001161206.1	Q5ST30-4A0A1U9X9B3
VARS2	NM_001167733.3 linkuse as main transcript	c.-220+156C>T	intron_variant		NP_001161205.1	Q5ST30-3B4E0K6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VARS2	ENST00000676266.1 linkuse as main transcript	c.-28+156C>T		intron_variant			NM_020442.6	ENSP00000502585.1		Q5ST30-1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42530

AN:

151948

Hom.:

6831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.309

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:

0.281

GnomAD3 exomes

AF:

0.312

AC:

5781

AN:

18528

Hom.:

967

AF XY:

0.317

AC XY:

3035

AN XY:

9578

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.390

Gnomad EAS exome

AF:

0.297

Gnomad SAS exome

AF:

0.275

Gnomad FIN exome

AF:

0.302

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.343

AC:

404390

AN:

1177694

Hom.:

71139

Cov.:

AF XY:

0.343

AC XY:

193490

AN XY:

564554

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.234

Gnomad4 ASJ exome

AF:

0.373

Gnomad4 EAS exome

AF:

0.227

Gnomad4 SAS exome

AF:

0.279

Gnomad4 FIN exome

AF:

0.386

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.308

GnomAD4 genome

AF:

0.280

AC:

42540

AN:

152066

Hom.:

6828

Cov.:

AF XY:

0.281

AC XY:

20881

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.124

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:

0.338

Hom.:

5652

Bravo

AF:

0.263

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 45% 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: 42. 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

6.3

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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