20-63406703-G-A
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_172107.4(KCNQ2):c.2560C>T(p.Arg854Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,602,648 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R854H) has been classified as Uncertain significance.
Frequency
Consequence
NM_172107.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ2 | NM_172107.4 | c.2560C>T | p.Arg854Cys | missense_variant | 17/17 | ENST00000359125.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ2 | ENST00000359125.7 | c.2560C>T | p.Arg854Cys | missense_variant | 17/17 | 1 | NM_172107.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152250Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000244 AC: 55AN: 225488Hom.: 2 AF XY: 0.000362 AC XY: 45AN XY: 124180
GnomAD4 exome AF: 0.000137 AC: 198AN: 1450280Hom.: 2 Cov.: 30 AF XY: 0.000198 AC XY: 143AN XY: 720946
GnomAD4 genome AF: 0.000112 AC: 17AN: 152368Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74510
ClinVar
Submissions by phenotype
KCNQ2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 04, 2023 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2019 | This alteration is classified as 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. - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 28, 2020 | This variant is associated with the following publications: (PMID: 24623842) - |
Complex neurodevelopmental disorder Other:1
not provided, no classification provided | literature only | Channelopathy-Associated Epilepsy Research Center | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at