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.1892T>C (p.Ile631Thr)

CA170457

143786 (ClinVar)

Gene: CDKL5

Condition: CDKL5 disorder

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: cf916b16-4fcd-40e2-96b2-4e26fb1d5f95

Approved on: 2022-08-25

Published on: 2022-09-06

HGVS expressions

NM_001323289.2:c.1892T>C

NM_001323289.2(CDKL5):c.1892T>C (p.Ile631Thr)

NC_000023.11:g.18604816T>C

CM000685.2:g.18604816T>C

NC_000023.10:g.18622936T>C

CM000685.1:g.18622936T>C

NC_000023.9:g.18532857T>C

NG_008475.1:g.184212T>C

ENST00000623535.2:c.1892T>C

ENST00000635828.1:c.1892T>C

ENST00000674046.1:c.1892T>C

ENST00000379989.6:c.1892T>C

ENST00000379996.7:c.1892T>C

ENST00000463994.4:c.1892T>C

ENST00000623535.1:n.1892T>C

NM_001037343.1:c.1892T>C

NM_003159.2:c.1892T>C

NM_001323289.1:c.1892T>C

NM_001037343.2:c.1892T>C

NM_003159.3:c.1892T>C

Benign

BA1 BP2 BS2

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 allele frequency of the p.Ile631Thr variant in CDKL5 is 0.03% in African sub population in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). The p.Ile631Thr variant is observed in at least 2 unaffected individuals (internal database) (BS2). The p.Ile631Thr variant is observed in the CDKL5 gene where a second pathogenic variant in the same gene is present in the patient (PMID 19793311) (BP2). In summary, the p.Ile631Thr variant in CDKL5 is classified as benign based on the ACMG/AMP criteria (BA1, BS2, BP2).

BA1

BP2

The p.Ile631Thr variant is observed in the CDKL5 gene where a second pathogenic variant in the same gene is present in the patient (PMID 19793311)

BS2

The p.Ile631Thr variant is observed in at least 2 unaffected individuals (internal database)

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