16-29813809-C-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_145239.3(PRRT2):āc.755C>Gā(p.Ala252Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,612,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_145239.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRRT2 | ENST00000358758.12 | c.755C>G | p.Ala252Gly | missense_variant | 2/4 | 1 | NM_145239.3 | ENSP00000351608.7 | ||
ENSG00000280893 | ENST00000609618.2 | n.755C>G | non_coding_transcript_exon_variant | 2/6 | 5 | ENSP00000476774.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249184Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135076
GnomAD4 exome AF: 0.0000240 AC: 35AN: 1460488Hom.: 0 Cov.: 35 AF XY: 0.0000262 AC XY: 19AN XY: 726562
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74308
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 21, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 21, 2019 | - - |
Episodic kinesigenic dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 02, 2024 | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 252 of the PRRT2 protein (p.Ala252Gly). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 506531). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2022 | The c.755C>G (p.A252G) alteration is located in exon 2 (coding exon 1) of the PRRT2 gene. This alteration results from a C to G substitution at nucleotide position 755, causing the alanine (A) at amino acid position 252 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at