chr7-6009433-ATG-A
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_006303.4(AIMP2):c.72_73del(p.Met24IlefsTer25) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000158 in 1,458,998 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
AIMP2
NM_006303.4 frameshift
NM_006303.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.29
Genes affected
AIMP2 (HGNC:20609): (aminoacyl tRNA synthetase complex interacting multifunctional protein 2) The protein encoded by this gene is part of the aminoacyl-tRNA synthetase complex, which contains nine different aminoacyl-tRNA synthetases and three non-enzymatic factors. The encoded protein is one of the non-enzymatic factors and is required for assembly and stability of the complex. [provided by RefSeq, May 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.926 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 7-6009433-ATG-A is Pathogenic according to our data. Variant chr7-6009433-ATG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 985778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-6009433-ATG-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AIMP2 | NM_006303.4 | c.72_73del | p.Met24IlefsTer25 | frameshift_variant | 1/4 | ENST00000223029.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AIMP2 | ENST00000223029.8 | c.72_73del | p.Met24IlefsTer25 | frameshift_variant | 1/4 | 1 | NM_006303.4 | P1 | |
AIMP2 | ENST00000395236.2 | c.72_73del | p.Met24IlefsTer51 | frameshift_variant | 1/3 | 2 | |||
AIMP2 | ENST00000400479.6 | c.-251+57_-251+58del | intron_variant | 5 | |||||
AIMP2 | ENST00000415999.1 | c.72_73del | p.Met24IlefsTer43 | frameshift_variant, NMD_transcript_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.0000158 AC: 23AN: 1458998Hom.: 0 AF XY: 0.0000152 AC XY: 11AN XY: 725804
GnomAD4 exome
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11
AN XY:
725804
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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Cov.:
32
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | May 15, 2018 | - - |
Leukodystrophy, hypomyelinating, 17 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center | Oct 03, 2022 | PVS1, PM2 - |
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