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.1892T>C (p.Ile631Thr)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

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 BS2 BP2

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

BS2

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

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)

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.