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_32dup(p.Ile8_Glu10dup) variant causes a 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 (★★). Synonymous variant affecting the same amino acid position (i.e. S5S) has been classified as Likely benign.
Frequency
Consequence
NM_145239.3 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRRT2 | NM_145239.3 | c.24_32dup | p.Ile8_Glu10dup | inframe_insertion | 2/4 | ENST00000358758.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRRT2 | ENST00000358758.12 | c.24_32dup | p.Ile8_Glu10dup | inframe_insertion | 2/4 | 1 | NM_145239.3 | P1 | |
MVP-DT | ENST00000569039.5 | n.246-2896_246-2895insATCTCAGAG | intron_variant, non_coding_transcript_variant | 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
Uncertain significance, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | May 21, 2020 | 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
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 14, 2023 | 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. This variant has not been reported in the literature in individuals affected with PRRT2-related conditions. 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. ClinVar contains an entry for this variant (Variation ID: 845093). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at