rs774002673
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM5PP2BP4BS1_SupportingBS2
The NM_172107.4(KCNQ2):c.2252C>T(p.Ser751Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000952 in 1,533,154 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S751A) has been classified as Likely pathogenic.
Frequency
Consequence
NM_172107.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ2 | NM_172107.4 | c.2252C>T | p.Ser751Leu | missense_variant | 17/17 | ENST00000359125.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ2 | ENST00000359125.7 | c.2252C>T | p.Ser751Leu | missense_variant | 17/17 | 1 | NM_172107.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000985 AC: 15AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000652 AC: 9AN: 138110Hom.: 0 AF XY: 0.0000656 AC XY: 5AN XY: 76258
GnomAD4 exome AF: 0.0000949 AC: 131AN: 1380930Hom.: 0 Cov.: 36 AF XY: 0.0000985 AC XY: 67AN XY: 680422
GnomAD4 genome AF: 0.0000985 AC: 15AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74358
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 751 of the KCNQ2 protein (p.Ser751Leu). This variant is present in population databases (rs774002673, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. ClinVar contains an entry for this variant (Variation ID: 339329). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Experimental studies have shown that this missense change affects KCNQ2 function (PMID: 35104249). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Developmental and epileptic encephalopathy, 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jul 03, 2020 | - - |
Complex neurodevelopmental disorder Other:1
not provided, no classification provided | literature only | Channelopathy-Associated Epilepsy Research Center | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at