NM_145239.3:c.971dupG
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_145239.3(PRRT2):c.971dupG(p.Val325SerfsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,206 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: 0.0000021 ( 0 hom. )
Consequence
PRRT2
NM_145239.3 frameshift
NM_145239.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.282
Publications
1 publications found
Genes affected
PRRT2 (HGNC:30500): (proline rich transmembrane protein 2) This gene encodes a transmembrane protein containing a proline-rich domain in its N-terminal half. Studies in mice suggest that it is predominantly expressed in brain and spinal cord in embryonic and postnatal stages. Mutations in this gene are associated with episodic kinesigenic dyskinesia-1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
ENSG00000280893 (HGNC:):
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 14 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 16 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-29814418-T-TG is Pathogenic according to our data. Variant chr16-29814418-T-TG is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 871891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_145239.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| PRRT2 | NM_145239.3 | MANE Select | c.971dupG | p.Val325SerfsTer16 | frameshift | Exon 3 of 4 | NP_660282.2 | Q7Z6L0-1 | |
| PRRT2 | NM_001256442.2 | c.971dupG | p.Val325SerfsTer15 | frameshift | Exon 3 of 3 | NP_001243371.1 | Q7Z6L0-2 | ||
| PRRT2 | NM_001438121.1 | c.971dupG | p.Val325SerfsTer15 | frameshift | Exon 3 of 3 | NP_001425050.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PRRT2 | ENST00000358758.12 | TSL:1 MANE Select | c.971dupG | p.Val325SerfsTer16 | frameshift | Exon 3 of 4 | ENSP00000351608.7 | Q7Z6L0-1 | |
| ENSG00000280893 | ENST00000609618.2 | TSL:5 | n.960dupG | non_coding_transcript_exon | Exon 3 of 6 | ENSP00000476774.2 | A0A0G2JLL6 | ||
| PRRT2 | ENST00000567659.3 | TSL:2 | c.971dupG | p.Val325SerfsTer15 | frameshift | Exon 3 of 3 | ENSP00000456226.1 | Q7Z6L0-2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000410 AC: 1AN: 243722 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
243722
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: 0.00000206 AC: 3AN: 1456206Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 724306 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
3
AN:
1456206
Hom.:
Cov.:
35
AF XY:
AC XY:
1
AN XY:
724306
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:
33380
American (AMR)
AF:
AC:
0
AN:
44040
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25698
East Asian (EAS)
AF:
AC:
1
AN:
39676
South Asian (SAS)
AF:
AC:
0
AN:
85528
European-Finnish (FIN)
AF:
AC:
0
AN:
52710
Middle Eastern (MID)
AF:
AC:
0
AN:
5736
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1109266
Other (OTH)
AF:
AC:
0
AN:
60172
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0706630), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
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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.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic/Likely pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
1
-
-
Episodic kinesigenic dyskinesia (1)
1
-
-
Episodic kinesigenic dyskinesia 1 (1)
1
-
-
not provided (1)
1
-
-
PRRT2-related disorder (1)
1
-
-
Seizures, benign familial infantile, 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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