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.1196A>C (p.Asn399Thr)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA170438

143770 (ClinVar)

Gene: CDKL5

Condition: CDKL5 disorder

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

Link to MONDO

UUID: a8ba6a85-7562-4d1c-8dc4-0145eb331856

Approved on: 2025-08-27

Published on: 2025-09-30

HGVS expressions

NM_001323289.2:c.1196A>C

NM_001323289.2(CDKL5):c.1196A>C (p.Asn399Thr)

NC_000023.11:g.18604120A>C

CM000685.2:g.18604120A>C

NC_000023.10:g.18622240A>C

CM000685.1:g.18622240A>C

NC_000023.9:g.18532161A>C

NG_008475.1:g.183516A>C

ENST00000623535.2:c.1196A>C

ENST00000635828.1:c.1196A>C

ENST00000637881.1:c.1196A>C

ENST00000674046.1:c.1196A>C

ENST00000379989.6:c.1196A>C

ENST00000379996.7:c.1196A>C

ENST00000463994.4:c.1196A>C

ENST00000623535.1:c.1196A>C

NM_001037343.1:c.1196A>C

NM_003159.2:c.1196A>C

NM_001323289.1:c.1196A>C

NM_001037343.2:c.1196A>C

NM_003159.3:c.1196A>C

Benign

BS1 BS2 BP4

PM2 PS4

Evidence Links 1

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 5.0.0

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 p.Asn399Thr variant in CDKL5 in gnomAD v4.1 is 0.0000156 in Non-Finnish European population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.0000083) for BS1, and therefore meets this criterion (BS1). The p.Asn399Thr variant in CDKL5 is observed in at least 2 unaffected individuals (internal database - GeneDx) (BS2). Computational analysis prediction tools suggest that the p.Asn399Thr variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Asn399Thr variant in CDKL5 is classified as benign based on the ACMG/AMP criteria (BS1, BS2, BP4). (CDKL5 Specifications v.5.0.0; curation approved on 8/27/2025)

BS1

BS2

The p.Asn399Thr variant is observed in at least 2 unaffected individuals (internal database - GeneDx).

BP4

Computational analysis prediction tools suggest that the p.Asn399Thr variant does not have a deleterious impact; however this information does not predict clinical significance on its own

PM2

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

PS4

The p.Asn399Thr variant has been observed in a female individual with infantile spasms and severe psychomotor delays (PMID 19253388); however the p.Asn399Thr is also present at a low frequency in the gnomAD database.

The p.Asn399Thr variant was observed a female individual with infantile spasms and severe psychomotor delays. The p.Asn399Thr variant was absent from the patient's mother but the father was not tested (PMID 19253388). PubMed:19253388

Curation History

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