Submissions for variant NM_001040142.2(SCN2A):c.4446+9A>G

dbSNP: rs796053140

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000189153	SCV000242785	likely pathogenic	not provided	2014-02-07	criteria provided, single submitter	clinical testing	c.4446+9 A>G: IVS24+9 A>G in intron 24 of the SCN2A gene (NM_021007.2). The c.4446+9 A>G nucleotide substitution has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In silico splice algorithms predict the c.4446+9 A>G sequence change may create a cryptic donor site that may lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of the c.4446+9 A>G substitution is unknown. This variant has been observed de novo without verified parentage. The variant is found in INFANT-EPI panel(s).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001214971	SCV001386684	pathogenic	Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11	2022-08-09	criteria provided, single submitter	clinical testing	This sequence change falls in intron 24 of the SCN2A gene. It does not directly change the encoded amino acid sequence of the SCN2A protein. This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 207002). This variant has been observed in individual(s) with SCN2A-related conditions (PMID: 29655203). In at least one individual the variant was observed to be de novo.