chr16-29813068-G-GCTCTGAGAT
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_145239.3(PRRT2):c.24_32dupCTCTGAGAT(p.Ile8_Glu10dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,658 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_145239.3 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRRT2 | ENST00000358758.12 | c.24_32dupCTCTGAGAT | p.Ile8_Glu10dup | disruptive_inframe_insertion | Exon 2 of 4 | 1 | NM_145239.3 | ENSP00000351608.7 | ||
ENSG00000280893 | ENST00000609618.2 | n.24_32dupCTCTGAGAT | non_coding_transcript_exon_variant | Exon 2 of 6 | 5 | ENSP00000476774.2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000820 AC: 2AN: 243874Hom.: 0 AF XY: 0.0000151 AC XY: 2AN XY: 132026
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1453658Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 723024
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Episodic kinesigenic dyskinesia 1 Uncertain:1
A heterozygous in-frame duplication variant was identified, NM_145239.2(PRRT2):c.24_32dup in exon 2 of 4 of the PRRT2 gene. This variant is predicted to result in an in-frame duplication of multiple amino acids at position 8 to 10 of the protein; NP_660282.2(PRRT2):p.(Ile8_Glu10dup). The amino acids at thess positions have overall low conservation (100 vertebrates, UCSC), and is not situated in a known functional domain (NCBI, PDB). The variant is present in the gnomAD population database at a frequency of 0.0008% (2 heterozygotes). The variant has not been previously reported in clinical cases. Based on information available at the time of curation, this variant has been classified as a VUS with LOW CLINICAL RELEVANCE. Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign -
Episodic kinesigenic dyskinesia Uncertain:1
This variant has not been reported in the literature in individuals affected with PRRT2-related conditions. This variant is present in population databases (rs757994031, gnomAD 0.002%). This variant, c.24_32dup, results in the insertion of 3 amino acid(s) of the PRRT2 protein (p.Ile8_Glu10dup), but otherwise preserves the integrity of the reading frame. ClinVar contains an entry for this variant (Variation ID: 845093). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at