16-23522468-G-GT
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
The NM_001083614.2(EARS2):c.*1902_*1903insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 147,486 control chromosomes in the GnomAD database, including 101 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.021 ( 101 hom., cov: 32)
Exomes 𝑓: 0.059 ( 0 hom. )
Consequence
EARS2
NM_001083614.2 3_prime_UTR
NM_001083614.2 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.646
Genes affected
EARS2 (HGNC:29419): (glutamyl-tRNA synthetase 2, mitochondrial) This gene encodes a member of the class I family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of glutamate to tRNA molecules. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency 12 (COXPD12). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0682 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EARS2 | NM_001083614.2 | c.*1902_*1903insA | 3_prime_UTR_variant | 9/9 | ENST00000449606.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EARS2 | ENST00000449606.7 | c.*1902_*1903insA | 3_prime_UTR_variant | 9/9 | 1 | NM_001083614.2 | P1 | ||
EARS2 | ENST00000674054.1 | c.*1809_*1810insA | 3_prime_UTR_variant, NMD_transcript_variant | 10/10 |
Frequencies
GnomAD3 genomes AF: 0.0214 AC: 3155AN: 147320Hom.: 101 Cov.: 32
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GnomAD4 exome AF: 0.0588 AC: 4AN: 68Hom.: 0 Cov.: 0 AF XY: 0.0250 AC XY: 1AN XY: 40
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GnomAD4 genome AF: 0.0215 AC: 3165AN: 147418Hom.: 101 Cov.: 32 AF XY: 0.0203 AC XY: 1461AN XY: 71902
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Combined oxidative phosphorylation deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at