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_001323289.2(CDKL5):c.1684A>G (p.Thr562Ala)

CA10360405

434666 (ClinVar)

Gene: CDKL5

Condition: CDKL5 disorder

Inheritance Mode: X-linked inheritance

Link to MONDO

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

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:n.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

PS4 PM1 PM2 BS1

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.Thr562Ala variant in CDKL5 is present in 1 female individual in gnomAD (0.001879%) (not sufficient to meet BS1 criteria). Computational analysis prediction tools suggest that the p.Thr562Ala variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). The p.Thr562Ala variant is observed in at least 2 unaffected individuals (internal database - Ambry Genetics, internal database - Invitae) (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).

BS2

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

BP4

Computational analysis prediction tools suggest that the p.Thr562Ala variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4).

PS4

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

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

BS1

The p.Thr562Ala variant in CDKL5 is present in 1 female individuals in gnomAD (0.001879%) (not sufficient to meet BS1 criteria).

Approved on: 2023-03-17

Published on: 2023-03-31

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