Evidence Repository - GenboreeKB

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_000330.4(RS1):c.185-3213A>C

Curation Version - 2.2
Curation History
JSON LD for Version 2.2

CA10360748

377651 (ClinVar)

Gene: CDKL5

Condition: CDKL5 disorder

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 90874f2e-7c69-4877-92a3-5140f63c71d6

Approved on: 2023-02-20

Published on: 2023-12-08

HGVS expressions

NM_000330.4:c.185-3213A>C

NM_000330.4(RS1):c.185-3213A>C

NC_000023.11:g.18650545T>G

CM000685.2:g.18650545T>G

NC_000023.10:g.18668665T>G

CM000685.1:g.18668665T>G

NC_000023.9:g.18578586T>G

NG_008475.1:g.229941T>G

NG_008659.3:g.31904A>C

ENST00000379984.4:c.185-3213A>C

ENST00000673617.1:n.205T>G

ENST00000379984.3:c.185-3213A>C

ENST00000379989.6:c.2933T>G

ENST00000379996.7:c.2933T>G

NM_000330.3:c.185-3213A>C

NM_001037343.1:c.2933T>G

NM_003159.2:c.2933T>G

NM_001037343.2:c.2933T>G

NM_003159.3:c.2933T>G

Likely Benign

BS1 BP4

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2

PDF

Criteria Specification Approval History

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 allele frequency of the c.2933T>G (p.Leu978Arg) variant in the CDKL5 transcript (NM_003159.2) (RS1 c.185-3213A>C) is 0.01184% in the European (non-Finnish) sub population in gnomAD, 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). Computational analysis prediction tools suggest that the p.Leu978Arg variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Leu978Arg variant in CDKL5 is classified as likely benign based on the ACMG/AMP criteria (BS1, BP4).

BS1

The allele frequency of the c.2933T>G (p.Leu978Arg) variant in the CDKL5 transcript (NM_003159.2) is 0.01184% in European (non-Finnish) sub population in gnomAD, 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.

BP4

Computational analysis prediction tools suggest that the p.Leu978Arg variant does not have a deleterious impact; however this information does not predict clinical significance on its own.

Curation History

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