ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.527G>A (p.Trp176Ter)

dbSNP: rs2147145565
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001382473 SCV001581248 pathogenic Developmental and epileptic encephalopathy, 2; Angelman syndrome-like 2020-05-27 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CDKL5 are known to be pathogenic (PMID: 22872100). This nonsense change has been observed in individual(s) with CDKL5-related conditions (PMID: 26544041, 28386848). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp176*) in the CDKL5 gene. It is expected to result in an absent or disrupted protein product.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV002243173 SCV002512422 likely pathogenic Developmental and epileptic encephalopathy, 2 2022-01-31 criteria provided, single submitter clinical testing ACMG classification criteria: PVS1 very strong, PM2 moderate
Centre for Population Genomics, CPG RCV005053983 SCV005687619 pathogenic CDKL5 disorder 2024-12-23 criteria provided, single submitter curation This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as pathogenic. At least the following criteria are met: Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). This variant has been identified as a de novo occurrence in at least 2 individuals with CDKL5 disorder, without confirmation of paternity and maternity (PM6_Strong). This variant is absent from gnomAD (PM2_Supporting).

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