16-29812324-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001256443.2(PRRT2):c.-93G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,220 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001256443.2 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRRT2 | ENST00000358758.12 | c.-66+1G>A | splice_donor_variant, intron_variant | Intron 1 of 3 | 1 | NM_145239.3 | ENSP00000351608.7 | |||
ENSG00000280893 | ENST00000609618.2 | n.-66+1G>A | splice_donor_variant, intron_variant | Intron 1 of 5 | 5 | ENSP00000476774.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 31
GnomAD4 exome Cov.: 0
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
not provided Uncertain:1
c.-66+1 G>A: IVS1+1 G>A in intron 1 of the PRRT2 gene (NM_145239.2)A variant of unknown significance has been identified in the PRRT2 gene. The c.-66+1 G>A variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The c.-66+1 G>A variant destroys the canonical splice donor site of non-coding exon 1, either leading to the inclusion of abnormal sequence into the 5' UTR or deletion of sequence normally included in the 5' UTR. However, to our knowledge, no regulatory mutations have been reported in the PRRT2 gene. Additionally, in the absence of RNA/functional studies, the actual effect of the c.-66+1 G>A sequence change is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at