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]

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Variant: NM_001323289.2(CDKL5):c.1064G>A (p.Arg355Gln)

CA10360343

423478 (ClinVar)

Gene: CDKL5

Condition: CDKL5 disorder

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: a7116a77-0031-4c0b-a786-be34fcc7373e

HGVS expressions

NM_001323289.2:c.1064G>A

NM_001323289.2(CDKL5):c.1064G>A (p.Arg355Gln)

NC_000023.11:g.18603988G>A

CM000685.2:g.18603988G>A

NC_000023.10:g.18622108G>A

CM000685.1:g.18622108G>A

NC_000023.9:g.18532029G>A

NG_008475.1:g.183384G>A

ENST00000623535.2:c.1064G>A

ENST00000635828.1:c.1064G>A

ENST00000637881.1:c.1064G>A

ENST00000674046.1:c.1064G>A

ENST00000379989.6:c.1064G>A

ENST00000379996.7:c.1064G>A

ENST00000463994.4:c.1064G>A

ENST00000623535.1:n.1064G>A

NM_001037343.1:c.1064G>A

NM_003159.2:c.1064G>A

NM_001323289.1:c.1064G>A

NM_001037343.2:c.1064G>A

NM_003159.3:c.1064G>A

Benign

BP5 BS1 BS2

PM1

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 allele frequency of the p.Arg355Gln variant in CDKL5 is 0.011% in African 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.Arg355Gln variant is observed in at least 2 unaffected individuals (internal database - GeneDx, internal database - Invitae) (BS2) and the variant is found in at least 2 patients with an alternate molecular basis of disease (internal database - GeneDx, internal database - Invitae) (BP5). In summary, the p.Arg355Gln variant in CDKL5 is classified as Benign for CDKL5-associated disorder based on the ACMG/AMP criteria (BS1, BS2, BP5).

BP5

The p.Arg355Gln variant is found in two patients with an alternate molecular basis of disease (internal database - Invitae, internal database - GeneDx).

BS1

The allele frequency of the p.Arg355Gln variant in CDKL54 is 0.011% in African 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.

BS2

The p.Arg355Gln variant is observed in at least 2 unaffected individuals (internal database - GeneDx, internal database - Invitae).

PM1

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

Approved on: 2023-02-20

Published on: 2023-03-31

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