rs1057518631
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_002488.5(NDUFA2):c.199delG(p.Ala67ProfsTer13) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000516 in 1,550,958 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A67A) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000050 ( 0 hom. )
Consequence
NDUFA2
NM_002488.5 frameshift
NM_002488.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.94
Publications
1 publications found
Genes affected
NDUFA2 (HGNC:7685): (NADH:ubiquinone oxidoreductase subunit A2) The encoded protein is a subunit of the hydrophobic protein fraction of the NADH:ubiquinone oxidoreductase (complex 1), the first enzyme complex in the electron transport chain located in the inner mitochondrial membrane, and may be involved in regulating complex I activity or its assembly via assistance in redox processes. Mutations in this gene are associated with Leigh syndrome, an early-onset progressive neurodegenerative disorder. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
IK (HGNC:5958): (IK cytokine) The protein encoded by this gene was identified by its RED repeat, a stretch of repeated arginine, glutamic acid and aspartic acid residues. The protein localizes to discrete dots within the nucleus, excluding the nucleolus. Its function is unknown. This gene maps to chromosome 5; however, a pseudogene may exist on chromosome 2. [provided by RefSeq, Jul 2008]
TMCO6 (HGNC:28814): (transmembrane and coiled-coil domains 6) Predicted to enable nuclear import signal receptor activity. Predicted to be involved in protein import into nucleus. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_002488.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NDUFA2 | NM_002488.5 | MANE Select | c.199delG | p.Ala67ProfsTer13 | frameshift | Exon 2 of 3 | NP_002479.1 | O43678-1 | |
| NDUFA2 | NM_001185012.2 | c.199delG | p.Ala67ProfsTer34 | frameshift | Exon 2 of 3 | NP_001171941.1 | O43678-2 | ||
| NDUFA2 | NR_033697.2 | n.366delG | non_coding_transcript_exon | Exon 1 of 2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NDUFA2 | ENST00000252102.9 | TSL:1 MANE Select | c.199delG | p.Ala67ProfsTer13 | frameshift | Exon 2 of 3 | ENSP00000252102.5 | O43678-1 | |
| NDUFA2 | ENST00000512088.1 | TSL:2 | c.199delG | p.Ala67ProfsTer34 | frameshift | Exon 2 of 3 | ENSP00000427220.1 | O43678-2 | |
| IK | ENST00000513256.5 | TSL:4 | c.-39delC | 5_prime_UTR | Exon 1 of 5 | ENSP00000425564.1 | D6RCQ4 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152132Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152132
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000500 AC: 7AN: 1398826Hom.: 0 Cov.: 30 AF XY: 0.00000872 AC XY: 6AN XY: 688424 show subpopulations
GnomAD4 exome
AF:
AC:
7
AN:
1398826
Hom.:
Cov.:
30
AF XY:
AC XY:
6
AN XY:
688424
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31702
American (AMR)
AF:
AC:
0
AN:
36986
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
21758
East Asian (EAS)
AF:
AC:
0
AN:
39186
South Asian (SAS)
AF:
AC:
0
AN:
75580
European-Finnish (FIN)
AF:
AC:
0
AN:
50730
Middle Eastern (MID)
AF:
AC:
0
AN:
5436
European-Non Finnish (NFE)
AF:
AC:
5
AN:
1079908
Other (OTH)
AF:
AC:
2
AN:
57540
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.439
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74318 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152132
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74318
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41416
American (AMR)
AF:
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5186
South Asian (SAS)
AF:
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68022
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (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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