chr12-32755515-T-TC
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001040436.3(YARS2):c.359dupG(p.Asp121ArgfsTer29) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000685 in 1,460,388 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
YARS2
NM_001040436.3 frameshift
NM_001040436.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.07
Publications
0 publications found
Genes affected
YARS2 (HGNC:24249): (tyrosyl-tRNA synthetase 2) This gene encodes a mitochondrial protein that catalyzes the attachment of tyrosine to tRNA(Tyr). Mutations in this gene are associated with myopathy with lactic acidosis and sideroblastic anemia type 2 (MLASA2). [provided by RefSeq, Jan 2011]
YARS2 Gene-Disease associations (from GenCC):
- myopathy, lactic acidosis, and sideroblastic anemia 2Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
- myopathy, lactic acidosis, and sideroblastic anemiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-32755515-T-TC is Pathogenic according to our data. Variant chr12-32755515-T-TC is described in ClinVar as Pathogenic. ClinVar VariationId is 209208.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001040436.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| YARS2 | NM_001040436.3 | MANE Select | c.359dupG | p.Asp121ArgfsTer29 | frameshift | Exon 1 of 5 | NP_001035526.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| YARS2 | ENST00000324868.13 | TSL:1 MANE Select | c.359dupG | p.Asp121ArgfsTer29 | frameshift | Exon 1 of 5 | ENSP00000320658.8 | ||
| YARS2 | ENST00000874023.1 | c.359dupG | p.Asp121ArgfsTer29 | frameshift | Exon 1 of 4 | ENSP00000544082.1 | |||
| YARS2 | ENST00000874022.1 | c.359dupG | p.Asp121ArgfsTer29 | frameshift | Exon 1 of 4 | ENSP00000544081.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000410 AC: 1AN: 243732 AF XY: 0.00000751 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
243732
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460388Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726560 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460388
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
726560
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33456
American (AMR)
AF:
AC:
0
AN:
44540
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26102
East Asian (EAS)
AF:
AC:
0
AN:
39680
South Asian (SAS)
AF:
AC:
0
AN:
86210
European-Finnish (FIN)
AF:
AC:
0
AN:
52682
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111606
Other (OTH)
AF:
AC:
0
AN:
60346
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
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0
1
1
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Myopathy, lactic acidosis, and sideroblastic anemia 2 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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