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]

Link to SEPIO compliant JSON-LD document

Variant: NM_001323289.2(CDKL5):c.872G>A (p.Cys291Tyr)

CA121527

11505 (ClinVar)

Gene: CDKL5

Condition: CDKL5 disorder

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: c8b52814-c9f3-44eb-962d-939b5420da52

HGVS expressions

NM_001323289.2:c.872G>A

NM_001323289.2(CDKL5):c.872G>A (p.Cys291Tyr)

NC_000023.11:g.18598508G>A

CM000685.2:g.18598508G>A

NC_000023.10:g.18616628G>A

CM000685.1:g.18616628G>A

NC_000023.9:g.18526549G>A

NG_008475.1:g.177904G>A

ENST00000623535.2:c.872G>A

ENST00000635828.1:c.872G>A

ENST00000637881.1:c.872G>A

ENST00000674046.1:c.872G>A

ENST00000379989.6:c.872G>A

ENST00000379996.7:c.872G>A

ENST00000463994.4:c.872G>A

ENST00000623535.1:n.872G>A

NM_001037343.1:c.872G>A

NM_003159.2:c.872G>A

NM_001323289.1:c.872G>A

NM_001037343.2:c.872G>A

NM_003159.3:c.872G>A

Uncertain Significance

PM6 PM2_Supporting PS4_Supporting

PP3 PM5 PM1 BS3 PS1 PS3

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

The p.Cys291Tyr variant in CDKL5 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with severe early-onset encephalopathy (PMID 18809835) (PM6). The p.Cys291Tyr variant in CDKL5 is absent from gnomAD (PM2_Supporting). The p.Cys291Tyr variant has been observed in at least 1 other individual with CDKL5-related disorder (PMID 18809835, PMID 25657822) (PS4_Supporting). In summary, the p.Cys291Tyr variant in CDKL5 is classified as a variant of unknown significance based on the ACMG/AMP criteria (PM6, PM2_Supporting, PS4_Supporting).

PM6

The p.Cys291Tyr variant in CDKL5 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with severe early-onset encephalopathy (PMID 18809835)

PM2_Supporting

The p.Cys291Tyr variant in CDKL5 is absent from gnomAD

PS4_Supporting

The p.Cys291Tyr variant has been observed in at least 1 other individual with CDKL5-related disorder (PMID 18809835, PMID 25657822)

PP3

REVEL score = 0.706

PM5

c.871T>C; p.C291R also reported but could not get higher than LPATH

PM1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2022-08-25

Published on: 2022-09-06

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