rs200877676
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting
The NM_145239.3(PRRT2):c.434G>A(p.Arg145Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R145W) has been classified as Likely benign.
Frequency
Consequence
NM_145239.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRRT2 | NM_145239.3 | c.434G>A | p.Arg145Gln | missense_variant | 2/4 | ENST00000358758.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRRT2 | ENST00000358758.12 | c.434G>A | p.Arg145Gln | missense_variant | 2/4 | 1 | NM_145239.3 | P1 | |
MVP-DT | ENST00000569039.5 | n.246-3315C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000725 AC: 11AN: 151700Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250096Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135354
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461440Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6AN XY: 726992
GnomAD4 genome ? AF: 0.0000725 AC: 11AN: 151818Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8AN XY: 74226
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 09, 2024 | Variant summary: PRRT2 c.434G>A (p.Arg145Gln) results in a conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 250096 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.434G>A in individuals affected with Episodic Kinesigenic Dyskinesia 1 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 568591). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Episodic kinesigenic dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 145 of the PRRT2 protein (p.Arg145Gln). This variant is present in population databases (rs200877676, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PRRT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 568591). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PRRT2 protein function with a negative predictive value of 95%. 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. - |
Seizures, benign familial infantile, 2;C1865926:Infantile convulsions and choreoathetosis;C4552000:Episodic kinesigenic dyskinesia 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 08, 2022 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 08, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at