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]

Variant: NM_003159.2(CDKL5):c.578A>G (p.Asp193Gly)

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Curation History
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CA171648

143826 (ClinVar)

Gene: CDKL5

Condition: CDKL5 disorder

Inheritance Mode: X-linked inheritance (dominant (HP:0001423))

Link to MONDO

UUID: ca9cd59d-d8f3-466f-a2e9-fa39541401c8

Approved on: 2021-03-26

Published on: 2021-05-17

HGVS expressions

NM_003159.2:c.578A>G

NM_003159.2(CDKL5):c.578A>G (p.Asp193Gly)

ENST00000623535.2:c.578A>G

ENST00000635828.1:c.578A>G

ENST00000637881.1:c.578A>G

ENST00000674046.1:c.578A>G

ENST00000379989.6:c.578A>G

ENST00000379996.7:c.578A>G

ENST00000463994.4:c.578A>G

ENST00000623535.1:n.578A>G

ENST00000623610.1:n.292A>G

NM_001037343.1:c.578A>G

NM_001323289.1:c.578A>G

NM_001323289.2:c.578A>G

NM_001037343.2:c.578A>G

NM_003159.3:c.578A>G

NC_000023.11:g.18587977A>G

CM000685.2:g.18587977A>G

NC_000023.10:g.18606097A>G

CM000685.1:g.18606097A>G

NC_000023.9:g.18516018A>G

NG_008475.1:g.167373A>G

Likely Pathogenic

PP1 PP4 PP3 PM2_Supporting PM6_Strong

PM5

Evidence Links 1

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.Asp193Gly variant in CDKL5 has been reported in at least 2 de novo occurrences (biological parentage unconfirmed) in affected individuals (PMID 23583054) (PM6_Strong). The p.Asp193Gly variant in CDKL5 is absent from gnomAD (PM2_Supporting). The variant has been reported to segregate in two informative meioses (PMID: 23583054) (PP1). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). The p.Asp193Gly variant in CDKL5 has been reported in an individual with a clinical phenotype suggestive of a CDKL5-associated disorder (PP4). In summary, the p.Asp193Gly variant in CDKL5 is classified as likely pathogenic for CDKL5-associated disorder based on the ACMG/AMP criteria (PM6_strong, PM2_supporting, PP1, PP3, PP4).

PP1

The variant has been reported to segregate in two informative meioses (PMID: 23583054)

The p.Asp193Gly variant has been reported to segregate in two affected family members with CDKL5 disorder. PubMed:23583054

PP4

The p.Asp193Gly variant in CDKL5 has been reported in an individual with a clinical phenotype suggestive of a CDKL5-associated disorder

PP3

Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own

PM2_Supporting

The p.Asp193Gly variant in CDKL5 is absent from gnomAD.

PM6_Strong

The p.Asp193Gly variant in CDKL5 has been reported in at least 2 de novo occurrences (biological parentage unconfirmed) in affected individuals (PMID 23583054)

PM5

Multiple missense variants have been previously identified within this codon (p.Asp193His and p.Asp193Asn); however these sequence variants do not meet the classification of pathogenic (PMID 27781031, 29655203).

Curation History

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