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_000330.4(RS1):c.326+1159C>G

Curation Version - 1.0
Curation History
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CA294768

156693 (ClinVar)

Gene: RS1

Condition: CDKL5 disorder

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 79063134-3f58-4b40-a321-214ea70c2fec

Approved on: 2023-04-14

Published on: 2023-06-16

HGVS expressions

NM_000330.4:c.326+1159C>G

NM_000330.4(RS1):c.326+1159C>G

NC_000023.11:g.18646032G>C

CM000685.2:g.18646032G>C

NC_000023.10:g.18664152G>C

CM000685.1:g.18664152G>C

NC_000023.9:g.18574073G>C

NG_008475.1:g.225428G>C

NG_008659.3:g.36417C>G

ENST00000379984.4:c.326+1159C>G

ENST00000379984.3:c.326+1159C>G

ENST00000379989.6:c.2739G>C

ENST00000379996.7:c.2739G>C

ENST00000476595.1:n.817+1159C>G

NM_000330.3:c.326+1159C>G

NM_001037343.1:c.2739G>C

NM_003159.2:c.2739G>C

NM_001037343.2:c.2739G>C

NM_003159.3:c.2739G>C

Likely Benign

BS2 BP4

PM2 BA1 BS1

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

RS1 (NM_000330.4) and an alternative transcript of CDKL5 (NM_003159.2) are overlapping transcripts; however, these variants are in the non-coding 3' region of the main CDKL5 transcript (NM_ 001323289.2). The c.2739 G>C (p.Gln913His) variant in CDKL5 transcript (NM_003159.3) (RS1 c.326+1159 C>G) is observed in at least 2 unaffected individuals (GeneDx and Invitae internal databases) (BS2). Computational analysis prediction tools suggest that the c.2739 G>C variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the c.2739 G>C variant in the alternate CDKL5 transcript (NM_003159.3) is classified as likely benign based on the ACMG/AMP criteria (BS2, BP4).

BS2

The c.2739 G>C variant is observed in at least 2 unaffected individuals (GeneDx and Invitae internal databases)

BP4

Computational analysis prediction tools suggest that the c.2739 G>C variant does not have a deleterious impact; however this information does not predict clinical significance on its own

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

BS1

The c.326+1159 C>G variant in CDKL5 is present in 2 female/male individual(s) in gnomAD (0.002%) (not sufficient to meet BS1 criteria).

Curation History

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