rs1270851643
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_172107.4(KCNQ2):c.31T>C(p.Tyr11His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,383,330 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000087 ( 0 hom. )
Consequence
KCNQ2
NM_172107.4 missense
NM_172107.4 missense
Scores
3
5
7
Clinical Significance
Conservation
PhyloP100: 2.64
Genes affected
KCNQ2 (HGNC:6296): (potassium voltage-gated channel subfamily Q member 2) The M channel is a slowly activating and deactivating potassium channel that plays a critical role in the regulation of neuronal excitability. The M channel is formed by the association of the protein encoded by this gene and a related protein encoded by the KCNQ3 gene, both integral membrane proteins. M channel currents are inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 1 (BFNC), also known as epilepsy, benign neonatal type 1 (EBN1). At least five transcript variants encoding five different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, KCNQ2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.31719282).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ2 | NM_172107.4 | c.31T>C | p.Tyr11His | missense_variant | 1/17 | ENST00000359125.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ2 | ENST00000359125.7 | c.31T>C | p.Tyr11His | missense_variant | 1/17 | 1 | NM_172107.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 0.00000867 AC: 12AN: 1383330Hom.: 0 Cov.: 32 AF XY: 0.00000877 AC XY: 6AN XY: 683888
GnomAD4 exome
AF:
AC:
12
AN:
1383330
Hom.:
Cov.:
32
AF XY:
AC XY:
6
AN XY:
683888
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2020 | In summary, this variant is a novel missense change with uncertain impact on protein function. 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"). While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a KCNQ2-related disease. This sequence change replaces tyrosine with histidine at codon 11 of the KCNQ2 protein (p.Tyr11His). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and histidine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L;.;.;.;.;L;L;L;L
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
Sift4G
Benign
T;T;T;T;T;T;T;T;T
Polyphen
P;.;.;.;.;P;P;P;.
Vest4
MutPred
Loss of phosphorylation at Y11 (P = 0.0419);Loss of phosphorylation at Y11 (P = 0.0419);Loss of phosphorylation at Y11 (P = 0.0419);Loss of phosphorylation at Y11 (P = 0.0419);Loss of phosphorylation at Y11 (P = 0.0419);Loss of phosphorylation at Y11 (P = 0.0419);Loss of phosphorylation at Y11 (P = 0.0419);Loss of phosphorylation at Y11 (P = 0.0419);Loss of phosphorylation at Y11 (P = 0.0419);
MVP
MPC
2.7
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at