rs2532938
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_020442.6(VARS2):c.3090+46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,612,636 control chromosomes in the GnomAD database, including 93,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.28 ( 6836 hom., cov: 33)
Exomes 𝑓: 0.34 ( 86675 hom. )
Consequence
VARS2
NM_020442.6 intron
NM_020442.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.54
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]
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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=-0.85).
BP6
?
Variant 6-30926054-G-A is Benign according to our data. Variant chr6-30926054-G-A is described in ClinVar as [Benign]. Clinvar id is 1292282.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 | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VARS2 | NM_020442.6 | c.3090+46G>A | intron_variant | ENST00000676266.1 | |||
VARS2 | NM_001167733.3 | c.2670+46G>A | intron_variant | ||||
VARS2 | NM_001167734.2 | c.3180+46G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VARS2 | ENST00000676266.1 | c.3090+46G>A | intron_variant | NM_020442.6 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.280 AC: 42555AN: 152038Hom.: 6839 Cov.: 33
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GnomAD3 exomes AF: 0.316 AC: 77861AN: 246172Hom.: 13166 AF XY: 0.324 AC XY: 43475AN XY: 134224
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GnomAD4 exome AF: 0.339 AC: 495623AN: 1460480Hom.: 86675 Cov.: 63 AF XY: 0.339 AC XY: 246421AN XY: 726516
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GnomAD4 genome ? AF: 0.280 AC: 42565AN: 152156Hom.: 6836 Cov.: 33 AF XY: 0.281 AC XY: 20883AN XY: 74378
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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 51% 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: 47. Only high quality variants are reported. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 23, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at