Variant 6-30914736-A-G 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.-101A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,393,526 control chromosomes in the GnomAD database, including 78,916 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6827 hom., cov: 32)

Exomes 𝑓: 0.33 ( 72089 hom. )

Consequence

VARS2
ENST00000321897.9 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.26

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-30914736-A-G is Benign according to our data. Variant chr6-30914736-A-G is described in ClinVar as [Benign]. Clinvar id is 1247754.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.-27-74A>G	intron_variant	ENST00000676266.1	NP_065175.4	Q5ST30-1B4E0K6B4DG77
VARS2	NM_001167734.2 linkuse as main transcript	c.59-69A>G	intron_variant		NP_001161206.1	Q5ST30-4A0A1U9X9B3
VARS2	NM_001167733.3 linkuse as main transcript	c.-220+392A>G	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.-27-74A>G		intron_variant			NM_020442.6	ENSP00000502585.1		Q5ST30-1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42526

AN:

152000

Hom.:

6830

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.307

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

GnomAD4 exome

AF:

0.335

AC:

415491

AN:

1241408

Hom.:

72089

Cov.:

AF XY:

0.334

AC XY:

205956

AN XY:

616452

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.370

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.272

Gnomad4 FIN exome

AF:

0.379

Gnomad4 NFE exome

AF:

0.352

Gnomad4 OTH exome

AF:

0.308

GnomAD4 genome

AF:

0.280

AC:

42536

AN:

152118

Hom.:

6827

Cov.:

AF XY:

0.281

AC XY:

20863

AN XY:

74364

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:

0.350

Hom.:

17208

Bravo

AF:

0.263

Asia WGS

AF:

0.207

AC:

724

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 44% 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: 41. 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

-0.91

CADD

Benign

0.035

DANN

Benign

0.62

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