Variant: NM_001323289.2(CDKL5):c.1768G>A (p.Glu590Lys)

CA10360416

680382 (ClinVar)

Gene: CDKL5

Condition: CDKL5 disorder

Inheritance Mode: X-linked inheritance

UUID: 05067df3-3a57-4067-95be-a1f6bd26509f

Approved on: 2023-03-17

Published on: 2023-03-31

HGVS expressions

NM_001323289.2:c.1768G>A
NM_001323289.2(CDKL5):c.1768G>A (p.Glu590Lys)
NC_000023.11:g.18604692G>A
CM000685.2:g.18604692G>A
NC_000023.10:g.18622812G>A
CM000685.1:g.18622812G>A
NC_000023.9:g.18532733G>A
NG_008475.1:g.184088G>A
ENST00000623535.2:c.1768G>A
ENST00000635828.1:c.1768G>A
ENST00000674046.1:c.1768G>A
ENST00000379989.6:c.1768G>A
ENST00000379996.7:c.1768G>A
ENST00000463994.4:c.1768G>A
ENST00000623535.1:n.1768G>A
NM_001037343.1:c.1768G>A
NM_003159.2:c.1768G>A
NM_001323289.1:c.1768G>A
NM_001037343.2:c.1768G>A
NM_003159.3:c.1768G>A

Benign

• Met criteria codes: BP5_Strong BS2 BS1

• Not Met criteria codes: BP4 PP3 PM1

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The allele frequency of the p.Glu590Lys variant in CDKL5 is 0.015% in Latino 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). Additionally, the p.Glu590Lys variant is observed in at least 14 unaffected individuals (internal database - GeneDx) (BS2) and at least 4 patients with an alternate molecular basis of disease (internal database - Invitae, internal database - GeneDx) (BP5_strong). In summary, the p.Glu590Lys variant in CDKL5 is classified as Benign for CDKL5-associated disorder based on the ACMG/AMP criteria (BS1, BS2, BP5_Strong).

Met criteria codes

• BP5_Strong: The p.Glu590Lys variant is found in at least 4 patients with an alternate molecular basis of disease (internal database - Invitae, internal database - GeneDx) (BP5_Strong).
• BS2: The p.Glu590Lys variant is observed in at least 2 unaffected individuals (internal database - GeneDx) (BS2).
• BS1: The allele frequency of the p.Glu590Lys variant in CDKL5 is 0.015% in Latino 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).

Not Met criteria codes

• BP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline