rs587777589
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_020745.4(AARS2):c.647delG(p.Gly216AlafsTer23) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_020745.4 frameshift
Scores
Clinical Significance
Conservation
Publications
- leukoencephalopathy, progressive, with ovarian failureInheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
- mitochondrial diseaseInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- combined oxidative phosphorylation defect type 8Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
- hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented gliaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- ovarioleukodystrophyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Pathogenic. The variant received 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AARS2 | NM_020745.4 | c.647delG | p.Gly216AlafsTer23 | frameshift_variant | Exon 4 of 22 | ENST00000244571.5 | NP_065796.2 | |
AARS2 | XM_005249245.4 | c.647delG | p.Gly216AlafsTer23 | frameshift_variant | Exon 4 of 20 | XP_005249302.1 | ||
AARS2 | XR_007059282.1 | n.671delG | non_coding_transcript_exon_variant | Exon 4 of 14 | ||||
LOC124901322 | XR_007059594.1 | n.301-3054delC | intron_variant | Intron 2 of 2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AARS2 | ENST00000244571.5 | c.647delG | p.Gly216AlafsTer23 | frameshift_variant | Exon 4 of 22 | 1 | NM_020745.4 | ENSP00000244571.4 | ||
ENSG00000272442 | ENST00000505802.1 | n.*449+3455delC | intron_variant | Intron 3 of 9 | 2 | ENSP00000424257.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461788Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727180 show subpopulations
GnomAD4 genome Cov.: 33
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at