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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC related information was provided by the message!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000330.4(RS1):c.326+1115G>A

CA327012012

464817 (ClinVar)

Gene: CDKL5
Condition: CDKL5 disorder
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 82ff382e-4eb6-4c3f-933e-5d62478948eb
Approved on: 2023-02-20
Published on: 2023-12-08

HGVS expressions

NM_000330.4:c.326+1115G>A
NM_000330.4(RS1):c.326+1115G>A
NC_000023.11:g.18646076C>T
CM000685.2:g.18646076C>T
NC_000023.10:g.18664196C>T
CM000685.1:g.18664196C>T
NC_000023.9:g.18574117C>T
NG_008475.1:g.225472C>T
NG_008659.3:g.36373G>A
ENST00000379984.4:c.326+1115G>A
ENST00000379984.3:c.326+1115G>A
ENST00000379989.6:c.2783C>T
ENST00000379996.7:c.2783C>T
ENST00000476595.1:n.817+1115G>A
NM_000330.3:c.326+1115G>A
NM_001037343.1:c.2783C>T
NM_003159.2:c.2783C>T
NM_001037343.2:c.2783C>T
NM_003159.3:c.2783C>T
More

Likely Benign

Met criteria codes 3
BS1 BP4 BS2_Supporting
Not Met criteria codes 1
PM1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
RS1(NM_000330.4) and an alternative transcript of CDKL5 (NM_003159.2) are overlapping transcripts; however, these variants are in the noncoding 3' region of the main CDKL5 transcript (NM_001323289.2). The c.2783C>T (p.Thr928Met) variant in CDKL5 transcript (NM_003159.2) (RS1 c.326+1115G>A) is 0.0188% 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). Computational analysis prediction tools suggest that the p.Thr928Met variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). Additionally, the p.Thr928Met variant is observed in at least 1 unaffected individual (PMID: 31209962) (BS2_supporting). In summary, the p.Thr928Met variant in CDKL5 (NM_003159.2) is classified as likely benign based on the ACMG/AMP criteria (BS1, BP4, BS2_supporting).
Met criteria codes
BS1
The allele frequency of the p.Thr928Met variant in CDKL5 is 0.0188% 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).
BP4
Computational analysis prediction tools suggest that the p.Thr928Met variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4).
BS2_Supporting
The p.Thr928Met variant is observed in at least 1 unaffected individual (PMID: 31209962) (BS2_supporting).
Not Met criteria codes
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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