rs35450031
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_172107.4(KCNQ2):c.1689C>T(p.Asp563=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000955 in 1,613,512 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0047 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00056 ( 5 hom. )
Consequence
KCNQ2
NM_172107.4 synonymous
NM_172107.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.95
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 20-63413524-G-A is Benign according to our data. Variant chr20-63413524-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 138026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63413524-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-1.95 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00475 (723/152320) while in subpopulation AFR AF= 0.0165 (686/41560). AF 95% confidence interval is 0.0155. There are 3 homozygotes in gnomad4. There are 339 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 718 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ2 | NM_172107.4 | c.1689C>T | p.Asp563= | synonymous_variant | 15/17 | ENST00000359125.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ2 | ENST00000359125.7 | c.1689C>T | p.Asp563= | synonymous_variant | 15/17 | 1 | NM_172107.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00472 AC: 718AN: 152202Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.00137 AC: 343AN: 251180Hom.: 2 AF XY: 0.00102 AC XY: 139AN XY: 135854
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GnomAD4 exome AF: 0.000560 AC: 818AN: 1461192Hom.: 5 Cov.: 32 AF XY: 0.000483 AC XY: 351AN XY: 726896
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 06, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 05, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 31, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 11, 2017 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 24, 2016 | 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 30, 2024 | - - |
Developmental and epileptic encephalopathy, 7 Other:1
not provided, no classification provided | literature only | GeneReviews | - | EE (epileptic encephalopathy) - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at