Submissions for variant NM_001271.4(CHD2):c.693-3C>A

dbSNP: rs2141785016

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002045161	SCV002296346	likely pathogenic	Developmental and epileptic encephalopathy 94	2021-01-11	criteria provided, single submitter	clinical testing	This sequence change falls in intron 7 of the CHD2 gene. It does not directly change the encoded amino acid sequence of the CHD2 protein. It affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of childhood-onset epileptic encephalopathy (Invitae). In at least one individual the variant was observed to be de novo. Nucleotide substitutions within 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 may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.