ClinVar Miner

Submissions for variant NM_000330.4(RS1):c.326+1115G>A

gnomAD frequency: 0.00005  dbSNP: rs951430019
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Total submissions: 3
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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 RCV003448321 SCV004176029 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 c.2783C>T (p.Thr928Met) variant in CDKL5 transcript (NM_003159.2) (RS1 c.326+1115G>A) is 0.0188% in African sub population in gnomAD, which is high enough to be classified as likely benign 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.Thr928Met variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). Additionally, the p.Thr928Met variant is observed in at least 1 unaffected individual (PMID: 31209962) (BS2_supporting). In summary, the p.Thr928Met variant in CDKL5 (NM_003159.2) is classified as likely benign based on the ACMG/AMP criteria (BS1, BP4, BS2_supporting).
Labcorp Genetics (formerly Invitae), Labcorp RCV000532113 SCV000639475 likely benign Developmental and epileptic encephalopathy, 2; Angelman syndrome-like 2024-04-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV002314982 SCV000847714 likely benign Inborn genetic diseases 2016-08-29 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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