chr20-63400695-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_172107.4(KCNQ2):c.*5949G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000499 in 398,640 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00044 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00054 ( 1 hom. )
Consequence
KCNQ2
NM_172107.4 3_prime_UTR
NM_172107.4 3_prime_UTR
Scores
1
6
Clinical Significance
Conservation
PhyloP100: -1.06
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0041336715).
BP6
?
Variant 20-63400695-C-T is Benign according to our data. Variant chr20-63400695-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2571140.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00044 (67/152350) while in subpopulation SAS AF= 0.00766 (37/4828). AF 95% confidence interval is 0.00572. There are 0 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 67 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ2 | NM_172107.4 | c.*5949G>A | 3_prime_UTR_variant | 17/17 | ENST00000359125.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ2 | ENST00000359125.7 | c.*5949G>A | 3_prime_UTR_variant | 17/17 | 1 | NM_172107.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000440 AC: 67AN: 152232Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.000536 AC: 132AN: 246290Hom.: 1 Cov.: 0 AF XY: 0.000633 AC XY: 79AN XY: 124818
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GnomAD4 genome ? AF: 0.000440 AC: 67AN: 152350Hom.: 0 Cov.: 33 AF XY: 0.000497 AC XY: 37AN XY: 74506
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | KCNQ2: BS1 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
Sift4G
Uncertain
T
Vest4
MVP
GERP RS
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at