Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
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Variant: NM_001323289.2(CDKL5):c.1311dup (p.Ser438fs)

CA170444

143774 (ClinVar)

Gene: CDKL5
Condition: CDKL5 disorder
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 12905ea2-5ad9-4efb-a505-4fac9bc22028
Approved on: 2024-04-18
Published on: 2024-07-31

HGVS expressions

NM_001323289.2:c.1311dup
NM_001323289.2(CDKL5):c.1311dup (p.Ser438fs)
NC_000023.11:g.18604235dup
CM000685.2:g.18604235dup
NC_000023.10:g.18622355dup
CM000685.1:g.18622355dup
NC_000023.9:g.18532276dup
NG_008475.1:g.183631dup
ENST00000623535.2:c.1311dup
ENST00000635828.1:c.1311dup
ENST00000637881.1:c.1311dup
ENST00000674046.1:c.1311dup
ENST00000379989.6:c.1311dup
ENST00000379996.7:c.1311dup
ENST00000463994.4:c.1311dup
ENST00000623535.1:c.1311dup
NM_001037343.1:c.1311dup
NM_003159.2:c.1311dup
NM_001323289.1:c.1311dup
NM_001037343.2:c.1311dup
NM_003159.3:c.1311dup

Pathogenic

Met criteria codes 3
PVS1 PM2_Supporting PM6

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CDKL5 Version 3.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The c.1311dup variant in CDKL5 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The c.1311dup variant in CDKL5 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with early onset seizures and infantile spasms (PMID 19793311) (PM6). The c.1311dup variant in CDKL5 is absent from gnomAD v2.1.1 (PM2_supporting). In summary, the c.1311dup variant in CDKL5 is classified as pathogenic for a CDKL5-related disorder based on the ACMG/AMP criteria (PVS1, PM6, PM2_supporting).
Met criteria codes
PVS1
The c.1311dup variant in CDKL5 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1).
PM2_Supporting
The c.1311dup variant in CDKL5 is absent from gnomAD v2.1.1.
PM6
The c.1311dup variant in CDKL5 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with early onset seizures and infantile spasms (PMID 19793311) (PM6).
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