rs1057516088
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PP2PP3_Strong
The NM_172107.4(KCNQ2):c.643G>A(p.Gly215Arg) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KCNQ2
NM_172107.4 missense
NM_172107.4 missense
Scores
11
3
1
Clinical Significance
Conservation
PhyloP100: 7.75
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
?
In a hotspot region, there are 15 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_172107.4
PP2
?
Missense variant where missense usually causes diseases, KCNQ2
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.978
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ2 | NM_172107.4 | c.643G>A | p.Gly215Arg | missense_variant | 4/17 | ENST00000359125.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ2 | ENST00000359125.7 | c.643G>A | p.Gly215Arg | missense_variant | 4/17 | 1 | NM_172107.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1435578Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 711132
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1435578
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
711132
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 7 Other:1
not provided, no classification provided | literature only | GeneReviews | - | Uncertain severity - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.;.;.;.;.;M;.;M;M;M;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
Sift4G
Pathogenic
D;D;D;D;D;.;D;D;D;D;D;D
Polyphen
D;.;.;.;.;.;D;.;D;D;.;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0523);Gain of MoRF binding (P = 0.0523);Gain of MoRF binding (P = 0.0523);Gain of MoRF binding (P = 0.0523);Gain of MoRF binding (P = 0.0523);.;Gain of MoRF binding (P = 0.0523);.;Gain of MoRF binding (P = 0.0523);Gain of MoRF binding (P = 0.0523);Gain of MoRF binding (P = 0.0523);.;
MVP
MPC
3.1
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