chr6-30921483-G-A

Variant names:

• chr6-30921483-G-A
• rs2517467
• NM_020442.6:c.1633-106G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020442.6(VARS2):​c.1633-106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 1,442,894 control chromosomes in the GnomAD database, including 218,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21794 hom., cov: 32)
  • Exomes 𝑓: 0.54 (196247 hom.)
• Consequence: VARS2 NM_020442.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.764

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-30921483-G-A is Benign according to our data. Variant chr6-30921483-G-A is described in ClinVar as [Benign]. Clinvar id is 1264235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VARS2	NM_020442.6	c.1633-106G>A		intron_variant	Intron 17 of 29	ENST00000676266.1	NP_065175.4
VARS2	NM_001167734.2	c.1723-106G>A		intron_variant	Intron 17 of 29		NP_001161206.1
VARS2	NM_001167733.3	c.1213-106G>A		intron_variant	Intron 16 of 28		NP_001161205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VARS2	ENST00000676266.1	c.1633-106G>A		intron_variant	Intron 17 of 29		NM_020442.6	ENSP00000502585.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79239 AN: 151908 Hom.: 21779 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.544 AC: 701678 AN: 1290868 Hom.: 196247 Cov.: 20 AF XY: 0.550 AC XY: 353011 AN XY: 642332

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.665

Gnomad4 ASJ exome AF: 0.617

Gnomad4 EAS exome AF: 0.803

Gnomad4 SAS exome AF: 0.730

Gnomad4 FIN exome AF: 0.638

Gnomad4 NFE exome AF: 0.514

Gnomad4 OTH exome AF: 0.555

GnomAD4 genome AF: 0.522 AC: 79289 AN: 152026 Hom.: 21794 Cov.: 32 AF XY: 0.534 AC XY: 39670 AN XY: 74328

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.521

Alfa AF: 0.531 Hom.: 15354

Bravo AF: 0.508

Asia WGS AF: 0.749 AC: 2607 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jul 31, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 81% 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: 75. Only high quality variants are reported. -

not provided Benign:1

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2517467; hg19: chr6-30889260;