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]
  • No CSPEC related information was provided by the message!
  • No Criteria Specification was provided in the publication event for the variant classifaction.
  • The Criteria Specification shown below is a best-estimate based on the VCEP, gene, disease, and publication date.

Variant: NM_001323289.2(CDKL5):c.291C>T (p.Leu97=)

CA10360246

748686 (ClinVar)

Gene: CDKL5 (HGNC:6792)
Condition: CDKL5 disorder (MONDO:0100039)
Inheritance Mode: X-linked inheritance
UUID: 6fb20210-ced8-47f1-ba35-7a2d754e4145
Approved on: 2022-09-01
Published on: 2022-09-06

HGVS expressions

NM_001323289.2:c.291C>T
NM_001323289.2(CDKL5):c.291C>T (p.Leu97=)
NC_000023.11:g.18579856C>T
CM000685.2:g.18579856C>T
NC_000023.10:g.18597976C>T
CM000685.1:g.18597976C>T
NC_000023.9:g.18507897C>T
NG_008475.1:g.159252C>T
ENST00000623535.2:c.291C>T
ENST00000635828.1:c.291C>T
ENST00000637881.1:c.291C>T
ENST00000674046.1:c.291C>T
ENST00000379989.6:c.291C>T
ENST00000379996.7:c.291C>T
ENST00000463994.4:c.291C>T
ENST00000623535.1:n.291C>T
NM_001037343.1:c.291C>T
NM_003159.2:c.291C>T
NM_001323289.1:c.291C>T
NM_001037343.2:c.291C>T
NM_003159.3:c.291C>T
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Benign

Met criteria codes 3
BS2 BS1 BP7
Not Met criteria codes 3
PM2 BA1 PP4

Evidence Links 0

Expert Panel

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.Leu97= variant in CDKL5 is 0.011% in African sub population in gnomAD, which is high enough to be classified as likely benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Leu97= variant is observed in at least 2 unaffected individuals (internal database) (BS2). The silent p.Leu97= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP7). The p.Leu97= variant in CDKL5 has been reported apparently homozygous in an individual with infantile epileptic encephalopathy (PMID 28454995); no criteria were applied for this case. In summary, the p.Leu97= variant in CDKL5 is classified as benign based on the ACMG/AMP criteria (BS1, BS2, BP7).
Met criteria codes
BS2
The p.Leu97= variant is observed in at least 2 unaffected individuals (internal database)
BS1
The allele frequency of the p.Leu97= variant in CDKL5 is 0.011% in African sub population in gnomAD, which is high enough to be classified as likely benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions.
BP7
The silent p.Leu97= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide
Not Met criteria codes
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
PMID 28454995: Patient ID:21, affected with infantile epileptic encephalopathy, reported homozygous for the p.L97= variant. Parental testing results not mentioned. Not applying any criteria. The p.Leu97= variant in CDKL5 has been reported apparently homozygous in an individual with infantile epileptic encephalopathy (PMID 28454995); no criteria were applied for this case.
Curation History
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