20-63408542-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_172107.4(KCNQ2):c.1764-6C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_172107.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Pathogenic:1
This sequence change falls in intron 15 of the KCNQ2 gene. It does not directly change the encoded amino acid sequence of the KCNQ2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with benign familial neonatal convulsions (PMID: 16686649). It has also been observed to segregate with disease in related individuals. This variant is also known as IVS14-6C>A, Val589X, and p.R588fsX589. ClinVar contains an entry for this variant (Variation ID: 21815). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects KCNQ2 function (PMID: 16686649). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. -
Seizures, benign familial neonatal, 1 Other:1
BFNE (benign familial neonatal epilepsy). In 1/11 seizures continued until 14 months of age; photosensitive myoclonic epilepsy at age 13 years. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at