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

CA121527

11505 (ClinVar)

Gene: CDKL5

Condition: CDKL5 disorder

Inheritance Mode: X-linked inheritance

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

Approved on: 2022-08-25

Published on: 2022-09-06

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

• Met criteria codes: PM6 PM2_Supporting PS4_Supporting

• Not Met criteria codes: PM5 PM1 PS1 PS3 PP3 BS3

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

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).

Met criteria codes

• 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)

Not Met criteria codes

• 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
• 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
• PP3: REVEL score = 0.706
• BS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline