chr2-178447553-CTA-C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5
The NM_003690.5(PRKRA):c.267_268delTA(p.His89GlnfsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 36)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
PRKRA
NM_003690.5 frameshift
NM_003690.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.04
Publications
3 publications found
Genes affected
PRKRA (HGNC:9438): (protein activator of interferon induced protein kinase EIF2AK2) This gene encodes a protein kinase activated by double-stranded RNA which mediates the effects of interferon in response to viral infection. Mutations in this gene have been associated with dystonia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]
PRKRA Gene-Disease associations (from GenCC):
- dystonia 16Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-178447553-CTA-C is Pathogenic according to our data. Variant chr2-178447553-CTA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 6347.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_003690.5. 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 |
|---|---|---|---|---|---|---|---|---|---|
| PRKRA | NM_003690.5 | MANE Select | c.267_268delTA | p.His89GlnfsTer22 | frameshift | Exon 3 of 8 | NP_003681.1 | ||
| PRKRA | NM_001139517.1 | c.234_235delTA | p.His78GlnfsTer22 | frameshift | Exon 2 of 7 | NP_001132989.1 | |||
| PRKRA | NM_001139518.1 | c.192_193delTA | p.His64GlnfsTer22 | frameshift | Exon 3 of 8 | NP_001132990.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PRKRA | ENST00000325748.9 | TSL:1 MANE Select | c.267_268delTA | p.His89GlnfsTer22 | frameshift | Exon 3 of 8 | ENSP00000318176.4 | ||
| PRKRA | ENST00000432031.6 | TSL:1 | c.234_235delTA | p.His78GlnfsTer22 | frameshift | Exon 2 of 7 | ENSP00000393883.2 | ||
| PRKRA | ENST00000487082.5 | TSL:1 | c.192_193delTA | p.His64GlnfsTer22 | frameshift | Exon 3 of 8 | ENSP00000430604.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
36
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251416 AF XY: 0.00000736 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251416
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461792Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727202 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1461792
Hom.:
AF XY:
AC XY:
1
AN XY:
727202
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33476
American (AMR)
AF:
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39682
South Asian (SAS)
AF:
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
AC:
0
AN:
53402
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111970
Other (OTH)
AF:
AC:
0
AN:
60388
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
36
EpiCase
AF:
EpiControl
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Dystonia 16 (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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