rs61746524
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_020442.6(VARS2):c.1514C>T(p.Ser505Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,613,870 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.013 ( 52 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 44 hom. )
Consequence
VARS2
NM_020442.6 missense
NM_020442.6 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 2.19
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 (MetaRNN=0.0051003397).
BP6
?
Variant 6-30921099-C-T is Benign according to our data. Variant chr6-30921099-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 381460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1965/152266) while in subpopulation AFR AF= 0.0449 (1866/41524). AF 95% confidence interval is 0.0432. There are 52 homozygotes in gnomad4. There are 859 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 52 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VARS2 | NM_020442.6 | c.1514C>T | p.Ser505Phe | missense_variant | 16/30 | ENST00000676266.1 | |
VARS2 | NM_001167734.2 | c.1604C>T | p.Ser535Phe | missense_variant | 16/30 | ||
VARS2 | NM_001167733.3 | c.1094C>T | p.Ser365Phe | missense_variant | 15/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VARS2 | ENST00000676266.1 | c.1514C>T | p.Ser505Phe | missense_variant | 16/30 | NM_020442.6 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0129 AC: 1961AN: 152148Hom.: 52 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00329 AC: 827AN: 251056Hom.: 16 AF XY: 0.00226 AC XY: 307AN XY: 135702
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GnomAD4 exome AF: 0.00125 AC: 1823AN: 1461604Hom.: 44 Cov.: 33 AF XY: 0.00100 AC XY: 727AN XY: 727104
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GnomAD4 genome ? AF: 0.0129 AC: 1965AN: 152266Hom.: 52 Cov.: 32 AF XY: 0.0115 AC XY: 859AN XY: 74438
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 19, 2017 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 15, 2016 | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.;D
REVEL
Benign
Sift
Uncertain
D;.;D
Sift4G
Uncertain
D;D;D
Polyphen
P;.;.
Vest4
MVP
MPC
0.88
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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