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.2200A>G (p.Thr734Ala)

CA171623

94108 (ClinVar)

Gene: CDKL5

Condition: CDKL5 disorder

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 1a422efe-2fba-45fc-8954-3129d753de2d

Approved on: 2022-09-01

Published on: 2022-09-06

HGVS expressions

NM_001323289.2:c.2200A>G

NM_001323289.2(CDKL5):c.2200A>G (p.Thr734Ala)

NC_000023.11:g.18613199A>G

CM000685.2:g.18613199A>G

NC_000023.10:g.18631319A>G

CM000685.1:g.18631319A>G

NC_000023.9:g.18541240A>G

NG_008475.1:g.192595A>G

ENST00000623535.2:c.2200A>G

ENST00000635828.1:c.2200A>G

ENST00000674046.1:c.2200A>G

ENST00000379989.6:c.2200A>G

ENST00000379996.7:c.2200A>G

ENST00000463994.4:c.2200A>G

ENST00000623535.1:n.2200A>G

NM_001037343.1:c.2200A>G

NM_003159.2:c.2200A>G

NM_001323289.1:c.2200A>G

NM_001037343.2:c.2200A>G

NM_003159.3:c.2200A>G

Likely Benign

BS2 BP5 BP4

PM6 PM2 BS1 BA1

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.Thr734Ala variant in CDKL5 is present in 7 female and male individuals in gnomAD (0.003%) (not sufficient to meet BS1 criteria). The p.Thr734Ala variant is observed in at least 2 unaffected individuals (internal database) (BS2). Computational analysis prediction tools suggest that the p.Thr734Ala variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). The p.Thr734Ala variant is found in a patient with an alternate molecular basis of disease (internal database) (BP5). In summary, the p.Thr734Ala variant in CDKL5 is classified as likely benign based on the ACMG/AMP criteria (BS2, BP4, BP5).

BS2

The p.Thr734Ala variant is observed in at least 2 unaffected individuals (internal database).

BP5

The p.Thr734Ala variant is found in a patient with an alternate molecular basis of disease (internal database)

BP4

Computational analysis prediction tools suggest that the p.Thr734Ala variant does not have a deleterious impact; however this information does not predict clinical significance on its own.

PM6

PMID: 23242510 - This variant is reported de novo (unconfirmed) in a female with seizures, delay, regression, gerd, abnormal EEG and brain MRI.

PM2

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

BS1

The p.Thr734Ala variant in CDKL5 is present in 7 female and male individuals in gnomAD (0.003%) (not sufficient to meet BS1 criteria).

BA1

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

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