rs1354411692
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_172107.4(KCNQ2):c.1324C>T(p.Arg442Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000025 in 1,601,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R442H) has been classified as Uncertain significance.
Frequency
Consequence
NM_172107.4 missense
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 |
---|---|---|---|---|---|---|---|
KCNQ2 | NM_172107.4 | c.1324C>T | p.Arg442Cys | missense_variant | 13/17 | ENST00000359125.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ2 | ENST00000359125.7 | c.1324C>T | p.Arg442Cys | missense_variant | 13/17 | 1 | NM_172107.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151390Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1450018Hom.: 0 Cov.: 35 AF XY: 0.00000139 AC XY: 1AN XY: 721936
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151390Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73870
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 20, 2018 | In summary, this variant has uncertain impact on KCNQ2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with a KCNQ2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 442 of the KCNQ2 protein (p.Arg442Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at