6-30914654-C-T

Position:

• chr6-30914654-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000321897.9(VARS2):​c.-183C>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 0.00481 in 1,043,288 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (78 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (52 hom.)
• Consequence: VARS2 ENST00000321897.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00700

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]

ENSG00000288473 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-30914654-C-T is Benign according to our data. Variant chr6-30914654-C-T is described in ClinVar as [Benign]. Clinvar id is 676459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VARS2	NM_020442.6	c.-27-156C>T		intron_variant		ENST00000676266.1	NP_065175.4
VARS2	NM_001167734.2	c.59-151C>T		intron_variant			NP_001161206.1
VARS2	NM_001167733.3	c.-220+310C>T		intron_variant			NP_001161205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VARS2	ENST00000676266.1	c.-27-156C>T		intron_variant			NM_020442.6	ENSP00000502585.1

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2954 AN: 152160 Hom.: 78 Cov.: 32

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00903

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0186

GnomAD4 exome AF: 0.00231 AC: 2058 AN: 891010 Hom.: 52 Cov.: 12 AF XY: 0.00206 AC XY: 913 AN XY: 444140

Gnomad4 AFR exome AF: 0.0678

Gnomad4 AMR exome AF: 0.00692

Gnomad4 ASJ exome AF: 0.000367

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000693

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000306

Gnomad4 OTH exome AF: 0.00627

GnomAD4 genome AF: 0.0194 AC: 2956 AN: 152278 Hom.: 78 Cov.: 32 AF XY: 0.0189 AC XY: 1408 AN XY: 74474

Gnomad4 AFR AF: 0.0660

Gnomad4 AMR AF: 0.00902

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0170 Hom.: 23

Bravo AF: 0.0228

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs3218831; hg19: chr6-30882431;