Evidence Repository - Clinical Genome Resources

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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Variant: NM_003159.2(CDKL5):c.1211_1212dupAC (p.Leu405Thrfs)

CA16621277

423029 (ClinVar)

Gene: CDKL5

Condition: CDKL5 disorder

Inheritance Mode: X-linked inheritance (dominant (HP:0001423))

Link to MONDO

UUID: 22973cbf-64a1-4e30-9dbf-9c3f3682b6c3

Approved on: 2021-03-26

Published on: 2021-05-17

HGVS expressions

NM_003159.2:c.1211_1212dupAC

NM_003159.2(CDKL5):c.1211_1212dupAC (p.Leu405Thrfs)

NC_000023.11:g.18604135_18604136dup

CM000685.2:g.18604135_18604136dup

NC_000023.10:g.18622255_18622256dup

CM000685.1:g.18622255_18622256dup

NC_000023.9:g.18532176_18532177dup

NG_008475.1:g.183531_183532dup

ENST00000623535.2:c.1211_1212dup

ENST00000635828.1:c.1211_1212dup

ENST00000637881.1:c.1211_1212dup

ENST00000674046.1:c.1211_1212dup

ENST00000379989.6:c.1211_1212dup

ENST00000379996.7:c.1211_1212dup

ENST00000463994.4:c.1211_1212dup

ENST00000623535.1:n.1211_1212dup

NM_001037343.1:c.1211_1212dup

NM_003159.2:c.1211_1212dup

NM_001323289.1:c.1211_1212dup

NM_001323289.2:c.1211_1212dup

NM_001037343.2:c.1211_1212dup

NM_003159.3:c.1211_1212dup

Pathogenic

PS4_Supporting PM2_Supporting PVS1

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Leu405Thrfs variant in CDKL5 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene in which loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). This variant has been detected in at least one individual with CDKL5 disorder (ClinVar) (PS4_supporting). This variant is absent from the gnomAD (PM2_supporting). In summary, the p.Leu405Thrfs variant in CDKL5 is classified as Pathogenic for CDKL5 disorder based on the ACMG/AMP criteria (PVS1, PM2_supporting, PS4_supporting).

PS4_Supporting

The p.(Leu405Thrfs*89) variant has been observed in at least 1 other individual with CDKL5-related disorder (ClinVar Variation ID 423029).

PM2_Supporting

The p.(Leu405Thrfs*89) variant in CDKL5 is absent from gnomAD

PVS1

The p.(Leu405Thrfs*89) 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.

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