20-63419626-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4BP6BS1BS2
The NM_172107.4(KCNQ2):c.1294C>T(p.Arg432Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000323 in 1,610,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R432H) has been classified as Likely benign.
Frequency
Consequence
NM_172107.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ2 | NM_172107.4 | c.1294C>T | p.Arg432Cys | missense_variant | 12/17 | ENST00000359125.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ2 | ENST00000359125.7 | c.1294C>T | p.Arg432Cys | missense_variant | 12/17 | 1 | NM_172107.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152258Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000328 AC: 8AN: 243560Hom.: 0 AF XY: 0.0000227 AC XY: 3AN XY: 132030
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1458330Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 725132
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152258Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74390
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 432 of the KCNQ2 protein (p.Arg432Cys). This variant is present in population databases (rs368720575, gnomAD 0.02%). This missense change has been observed in individual(s) with epilepsy (PMID: 31199083). ClinVar contains an entry for this variant (Variation ID: 575399). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 03, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at