Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
Link to SEPIO compliant JSON-LD document
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_001323289.2(CDKL5):c.1721C>T (p.Pro574Leu)

CA294755

156685 (ClinVar)

Gene: CDKL5
Condition: CDKL5 disorder
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: f022babb-f253-476c-9120-ffdabaa396f7
Approved on: 2024-02-23
Published on: 2024-07-31

HGVS expressions

NM_001323289.2:c.1721C>T
NM_001323289.2(CDKL5):c.1721C>T (p.Pro574Leu)
NC_000023.11:g.18604645C>T
CM000685.2:g.18604645C>T
NC_000023.10:g.18622765C>T
CM000685.1:g.18622765C>T
NC_000023.9:g.18532686C>T
NG_008475.1:g.184041C>T
ENST00000623535.2:c.1721C>T
ENST00000635828.1:c.1721C>T
ENST00000674046.1:c.1721C>T
ENST00000379989.6:c.1721C>T
ENST00000379996.7:c.1721C>T
ENST00000463994.4:c.1721C>T
ENST00000623535.1:c.1721C>T
NM_001037343.1:c.1721C>T
NM_003159.2:c.1721C>T
NM_001323289.1:c.1721C>T
NM_001037343.2:c.1721C>T
NM_003159.3:c.1721C>T

Benign

Met criteria codes 3
BP5_Strong BS2 BS1
Not Met criteria codes 2
BP4 PP3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CDKL5 Version 3.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The allele frequency of the p.Pro574Leu variant in CDKL5 is 0.021% in European (Finnish) sub population in gnomAD v2, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Pro574Leu variant is observed in the hemizygous state in at least 2 unaffected individuals (internal database - GeneDx) (BS2). The p.Pro574Leu variant is found in at least 3 patients with an alternate molecular basis of disease (internal database - GeneDx, internal database - Invitae) (BP5_strong). In summary, the p.Pro574Leu variant in CDKL5 is classified as benign based on the ACMG/AMP criteria (BS1, BS2, BP5_strong).
Met criteria codes
BP5_Strong
The p.Pro574Leu variant is found in at least 3 patients with an alternate molecular basis of disease (internal database - GeneDx, internal database - Invitae) (BP5_strong).
BS2
The p.Pro574Leu variant is observed in the hemizygous state in at least 2 unaffected individuals (internal database - GeneDx) (BS2).
BS1
The allele frequency of the p.Pro574Leu variant in CDKL5 is 0.021% in European (Finnish) sub population in gnomAD v2, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1).
Not Met criteria codes
BP4
Computational prediction analysis tools are inconclusive for this variant (no criteria applied).
PP3
Computational prediction analysis tools are inconclusive for this variant (no criteria applied).
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.
¤ Powered by BCM's Genboree.