rs745594874
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM5BP4_StrongBP6BS2
The NM_145239.3(PRRT2):āc.640G>Cā(p.Ala214Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000802 in 1,355,752 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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. A214G) has been classified as Uncertain significance.
Frequency
Consequence
NM_145239.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRRT2 | NM_145239.3 | c.640G>C | p.Ala214Pro | missense_variant | 2/4 | ENST00000358758.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRRT2 | ENST00000358758.12 | c.640G>C | p.Ala214Pro | missense_variant | 2/4 | 1 | NM_145239.3 | P1 | |
MVP-DT | ENST00000569039.5 | n.246-3521C>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 137AN: 149504Hom.: 2 Cov.: 31 FAILED QC
GnomAD3 exomes AF: 0.00152 AC: 206AN: 135540Hom.: 0 AF XY: 0.00165 AC XY: 121AN XY: 73520
GnomAD4 exome AF: 0.000802 AC: 1087AN: 1355752Hom.: 1 Cov.: 36 AF XY: 0.000836 AC XY: 562AN XY: 672552
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.000909 AC: 136AN: 149604Hom.: 2 Cov.: 31 AF XY: 0.000876 AC XY: 64AN XY: 73022
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 22, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 14, 2020 | This variant is associated with the following publications: (PMID: 23496026, 27123484, 22101681, 26598493, 24594579, 27907910, 31124310) - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | PRRT2: BP4, BS1, BS2 - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 19, 2021 | - - |
Episodic kinesigenic dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 19, 2018 | 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. - |
PRRT2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 19, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at