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]

Variant: NM_001323289.2(CDKL5):c.1684A>G (p.Thr562Ala)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA10360405

434666 (ClinVar)

Gene: CDKL5

Condition: CDKL5 disorder

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 86cd6c81-4350-4b94-9e7b-7b0ae0934344

Approved on: 2025-02-28

Published on: 2025-03-28

HGVS expressions

NM_001323289.2:c.1684A>G

NM_001323289.2(CDKL5):c.1684A>G (p.Thr562Ala)

NC_000023.11:g.18604608A>G

CM000685.2:g.18604608A>G

NC_000023.10:g.18622728A>G

CM000685.1:g.18622728A>G

NC_000023.9:g.18532649A>G

NG_008475.1:g.184004A>G

ENST00000623535.2:c.1684A>G

ENST00000635828.1:c.1684A>G

ENST00000674046.1:c.1684A>G

ENST00000379989.6:c.1684A>G

ENST00000379996.7:c.1684A>G

ENST00000463994.4:c.1684A>G

ENST00000623535.1:c.1684A>G

NM_001037343.1:c.1684A>G

NM_003159.2:c.1684A>G

NM_001323289.1:c.1684A>G

NM_001037343.2:c.1684A>G

NM_003159.3:c.1684A>G

Likely Benign

BS2 BP4

BS1 PS4 PM1 PM2

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

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 highest population minor allele frequency of the c.1684A>G (p.Thr562Ala) variant in CDKL5 in gnomAD v4.1 is 0.000004 in the European (Non-Finnish) population (not sufficient to meet BS1 criteria). The computational predictor REVEL gives a score of 0.133, evidence that does not predict a damaging effect on CDKL5 function (BP4). The p.Thr562Ala variant is observed in at least 2 unaffected individuals (Ambry Genetics: internal database, Labcorp Genetics Inc. (formerly Invitae): internal database) (BS2). In summary, the p.Thr562Ala variant in CDKL5 is classified as Likely Benign for CDKL5-associated disorder based on the ACMG/AMP criteria (BP4, BS2) (CDKL5 Specifications v.3.0; curation approved on 02/28/2025).

BS2

The p.Thr562Ala variant is observed in at least 2 unaffected individuals (internal database - Ambry Genetics, internal database - Labcorp Genetics Inc (formerly Invitae)) (BS2).

BP4

The computational predictor REVEL gives a score of 0.133, evidence that does not predict a damaging effect on CDKL5 function (BP4).

BS1

The highest population minor allele frequency of the p.Thr562Ala variant in CDKL5 in gnomAD v4.1 is 0.000004 in the European (Non-Finnish) population (not sufficient to meet BS1 criteria).

PS4

The p.Thr562Ala variant is not currently published and is not present in additional databases (internal and publicly available), therefore, no additional criteria are applicable at this time.

PM1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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