rs376327268
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_172107.4(KCNQ2):c.2244C>T(p.His748=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000785 in 1,527,714 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000069 ( 0 hom. )
Consequence
KCNQ2
NM_172107.4 synonymous
NM_172107.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0250
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=-0.66).
BP6
?
Variant 20-63407019-G-A is Benign according to our data. Variant chr20-63407019-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 378031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.025 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000164 (25/152220) while in subpopulation AFR AF= 0.000531 (22/41466). AF 95% confidence interval is 0.000359. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 25 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ2 | NM_172107.4 | c.2244C>T | p.His748= | synonymous_variant | 17/17 | ENST00000359125.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ2 | ENST00000359125.7 | c.2244C>T | p.His748= | synonymous_variant | 17/17 | 1 | NM_172107.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152220Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000591 AC: 8AN: 135364Hom.: 0 AF XY: 0.0000536 AC XY: 4AN XY: 74606
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GnomAD4 exome AF: 0.0000691 AC: 95AN: 1375494Hom.: 0 Cov.: 36 AF XY: 0.0000724 AC XY: 49AN XY: 677194
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GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152220Hom.: 0 Cov.: 34 AF XY: 0.000148 AC XY: 11AN XY: 74358
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 09, 2015 | 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. - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2020 | - - |
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