rs772867219
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_015836.4(WARS2):c.298_300del(p.Leu100del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
WARS2
NM_015836.4 inframe_deletion
NM_015836.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.70
Genes affected
WARS2 (HGNC:12730): (tryptophanyl tRNA synthetase 2, mitochondrial) Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Two forms of tryptophanyl-tRNA synthetase exist, a cytoplasmic form, named WARS, and a mitochondrial form, named WARS2. This gene encodes the mitochondrial tryptophanyl-tRNA synthetase. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_015836.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 1-119076397-CAAG-C is Pathogenic according to our data. Variant chr1-119076397-CAAG-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 440916.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Pathogenic=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WARS2 | NM_015836.4 | c.298_300del | p.Leu100del | inframe_deletion | 2/6 | ENST00000235521.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WARS2 | ENST00000235521.5 | c.298_300del | p.Leu100del | inframe_deletion | 2/6 | 1 | NM_015836.4 | P1 | |
WARS2 | ENST00000369426.9 | c.298_300del | p.Leu100del | inframe_deletion | 2/6 | 1 | |||
WARS2 | ENST00000495746.5 | n.308_310del | non_coding_transcript_exon_variant | 2/5 | 2 | ||||
WARS2 | ENST00000497402.1 | n.410_412del | non_coding_transcript_exon_variant | 2/5 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
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GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250946Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135596
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461876Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727238
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:3Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | Mar 20, 2020 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 18, 2022 | - - |
Parkinsonism-dystonia 3, childhood-onset Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 18, 2022 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 15, 2017 | - - |
Computational scores
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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