Submissions for variant NM_000330.4(RS1):c.185-3213A>C

gnomAD frequency: 0.00009  dbSNP: rs143243059

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV003448304	SCV004176032	likely benign	CDKL5 disorder	2023-02-20	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 noncoding 3' region of the main CDKL5 transcript (NM_001323289.2). The allele frequency of the c.2933T>G (p.Leu978Arg) variant in the CDKL5 transcript (NM_003159.2) (RS1 c.185-3213A>C) is 0.01184% in the European (non-Finnish) sub population in gnomAD, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). Computational analysis prediction tools suggest that the p.Leu978Arg variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Leu978Arg variant in CDKL5 is classified as likely benign based on the ACMG/AMP criteria (BS1, BP4).
GeneDx	RCV000640497	SCV000512559	likely benign	not provided	2020-10-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001497485	SCV001702215	likely benign	Developmental and epileptic encephalopathy, 2; Angelman syndrome-like	2024-10-22	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001821157	SCV002066974	uncertain significance	not specified	2017-09-29	criteria provided, single submitter	clinical testing