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.1196A>C (p.Asn399Thr)

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: 2021-04-02

Published on: 2021-05-17

HGVS expressions

NM_003159.2:c.1196A>C

NM_003159.2(CDKL5):c.1196A>C (p.Asn399Thr)

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:n.1196A>C

NM_001037343.1:c.1196A>C

NM_001323289.1:c.1196A>C

NM_001323289.2:c.1196A>C

NM_001037343.2:c.1196A>C

NM_003159.3:c.1196A>C

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

Likely Benign

BP4 BS2

PS4 PM2

Evidence Links 1

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.Asn399Thr variant in CDKL5 is observed in at least 2 unaffected individuals (internal database) (BS2). This variant is also present in the heterozygous state in two individuals in gnomAD. 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 likely benign based on the ACMG/AMP criteria (BS2, BP4).

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

BS2

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

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

PM2

The p.Asn399Thr variant in CDKL5 is not absent from gnomAD (present in two heterozygotes).

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