Submissions for variant NM_172107.4(KCNQ2):c.1887+5G>A

gnomAD frequency: 0.00004  dbSNP: rs777916008

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000416080	SCV000333183	uncertain significance	not provided	2015-08-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000416080	SCV000493666	uncertain significance	not provided	2016-07-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000416080	SCV000565096	uncertain significance	not provided	2020-07-02	criteria provided, single submitter	clinical testing	Intronic +5 splice site variant in a gene for which loss-of-function is a known mechanism of disease, and both splice predictors and evolutionary conservation support a deleterious effect, although in the absence of functional evidence the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 23360469, 28717674, 29655203, 20437616)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001313507	SCV001504004	likely pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2024-03-26	criteria provided, single submitter	clinical testing	This sequence change falls in intron 16 of the KCNQ2 gene. It does not directly change the encoded amino acid sequence of the KCNQ2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs777916008, gnomAD 0.005%). This variant has been observed in individuals with early onset seizures (PMID: 23360469, 29655203; Invitae). ClinVar contains an entry for this variant (Variation ID: 282026). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Revvity Omics, Revvity	RCV000416080	SCV003811986	uncertain significance	not provided	2023-01-11	criteria provided, single submitter	clinical testing
GeneReviews	RCV000678201	SCV000484650	not provided	Seizures, benign familial neonatal, 1		no assertion provided	literature only	BFNIS (benign familial neonatal-infantile seizures); FS (febrile seizures)
Diagnostic Laboratory, Strasbourg University Hospital	RCV002275006	SCV002562815	uncertain significance	Seizure		no assertion criteria provided	clinical testing