Variant 6-30914729-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000321897.9(VARS2):c.-108T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,358,698 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 17 hom. )

Consequence

VARS2
ENST00000321897.9 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.00

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-30914729-T-C is Benign according to our data. Variant chr6-30914729-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1197970.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
VARS2	NM_020442.6 linkuse as main transcript	c.-27-81T>C	intron_variant	ENST00000676266.1	NP_065175.4	Q5ST30-1B4E0K6B4DG77
VARS2	NM_001167734.2 linkuse as main transcript	c.59-76T>C	intron_variant		NP_001161206.1	Q5ST30-4A0A1U9X9B3
VARS2	NM_001167733.3 linkuse as main transcript	c.-220+385T>C	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.-27-81T>C		intron_variant			NM_020442.6	ENSP00000502585.1		Q5ST30-1

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

386

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0257

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.00145

AC:

1750

AN:

1206380

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

841

AN XY:

599290

show subpopulations

Gnomad4 AFR exome

AF:

0.0000733

Gnomad4 AMR exome

AF:

0.0000690

Gnomad4 ASJ exome

AF:

0.0000485

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0250

Gnomad4 NFE exome

AF:

0.000650

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00253

AC:

386

AN:

152318

Hom.:

Cov.:

AF XY:

0.00350

AC XY:

261

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0257

Gnomad4 NFE

AF:

0.00159

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00270

Hom.:

Bravo

AF:

0.000427

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.28

DANN

Benign

0.56

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