ClinVar Miner

Submissions for variant NM_000330.4(RS1):c.184+3119G>A

gnomAD frequency: 0.00002  dbSNP: rs762576315
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel RCV003448358 SCV004176226 benign CDKL5 disorder 2023-12-06 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.3083C>T (p.Thr1028Met) variant in CDKL5 transcript (NM_003159.2) (RS1 c.184+3119G>A) is 0.046% in the Middle Eastern sub population in gnomAD v4, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). Computational analysis prediction tools suggest that the p.Thr1028Met variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). Additionally, the p.Thr1028Met variant is observed in at least 20 unaffected individuals (internal database - Invitae, internal database - GeneDx) (BS2) and at least 7 patients with an alternate molecular basis of disease (internal database – Ambry Genetics, internal database - Invitae, internal database - GeneDx) (BP5_Strong). In summary, the p.Thr1028Met variant in CDKL5 (NM_003159.2) is classified as Benign based on the ACMG/AMP criteria (BA1, BP4, BS2, BP5_Strong).
CeGaT Center for Human Genetics Tuebingen RCV000999343 SCV001155916 uncertain significance not provided 2016-05-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001066908 SCV001231931 likely benign Developmental and epileptic encephalopathy, 2; Angelman syndrome-like 2025-01-16 criteria provided, single submitter clinical testing
GeneDx RCV000999343 SCV001783813 likely benign not provided 2020-01-08 criteria provided, single submitter clinical testing

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