Submissions for variant NM_001040142.2(SCN2A):c.4551+10A>G

gnomAD frequency: 0.00004  dbSNP: rs767957352

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001418796	SCV001621035	likely benign	Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11	2025-02-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003388012	SCV004100254	likely benign	not specified	2023-09-28	criteria provided, single submitter	clinical testing	Variant summary: SCN2A c.4551+10A>G alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 5.4e-06 in 184590 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4551+10A>G in individuals affected with Early Infantile Epileptic Encephalopathy 11 and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.