Submissions for variant NM_000330.4(RS1):c.326+1159C>G

gnomAD frequency: 0.00001  dbSNP: rs587783160

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV003235064	SCV003933690	likely benign	CDKL5 disorder	2023-04-14	reviewed by expert panel	curation	RS1 (NM_000330.4) and an alternative transcript of CDKL5 (NM_003159.2) are overlapping transcripts; however, these variants are in the non-coding 3' region of the main CDKL5 transcript (NM_ 001323289.2). The c.2739 G>C (p.Gln913His) variant in CDKL5 transcript (NM_003159.3) (RS1 c.326+1159 C>G) is observed in at least 2 unaffected individuals (GeneDx and Invitae internal databases) (BS2). Computational analysis prediction tools suggest that the c.2739 G>C variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the c.2739 G>C variant in the alternate CDKL5 transcript (NM_003159.3) is classified as likely benign based on the ACMG/AMP criteria (BS2, BP4).
GeneDx	RCV001704065	SCV000191078	likely benign	not provided	2018-04-02	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000764871	SCV000896027	uncertain significance	Developmental and epileptic encephalopathy, 2	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV001202850	SCV001373981	likely benign	Developmental and epileptic encephalopathy, 2; Angelman syndrome-like	2023-10-09	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004544331	SCV004764735	likely benign	CDKL5-related disorder	2023-09-25	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).