Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_001323289.2(CDKL5):c.146-1G>A

CA171613

158179 (ClinVar)

Gene: CDKL5
Condition: CDKL5 disorder
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 0305323e-a1e9-44ca-a970-405bbb93be98
Approved on: 2024-06-25
Published on: 2024-07-31

HGVS expressions

NM_001323289.2:c.146-1G>A
NM_001323289.2(CDKL5):c.146-1G>A
NC_000023.11:g.18575353G>A
CM000685.2:g.18575353G>A
NC_000023.10:g.18593473G>A
CM000685.1:g.18593473G>A
NC_000023.9:g.18503394G>A
NG_008475.1:g.154749G>A
ENST00000623535.2:c.146-1G>A
ENST00000635828.1:c.146-1G>A
ENST00000637881.1:c.146-1G>A
ENST00000674046.1:c.146-1G>A
ENST00000379989.6:c.146-1G>A
ENST00000379996.7:c.146-1G>A
ENST00000463994.4:c.146-1G>A
ENST00000623364.3:c.146-1G>A
ENST00000623535.1:c.146-1G>A
ENST00000624700.3:c.146-1G>A
NM_001037343.1:c.146-1G>A
NM_003159.2:c.146-1G>A
NM_001323289.1:c.146-1G>A
NM_001037343.2:c.146-1G>A
NM_003159.3:c.146-1G>A
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Pathogenic

Met criteria codes 4
PP4 PM2_Supporting PM6_Strong PVS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CDKL5 Version 3.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The c.146-1G>A variant in CDKL5 (NM_001323289.2) is absent from gnomAD v2 (PM2_supporting). The c.146-1G>A variant in CDKL5 is predicted to affect a canonical splice site and lead to a truncated or absent protein in a CDKL5 where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The c.146-1G>A variant has been reported in an individual with a clinical phenotype suggestive of CDKL5 disorder (internal database - International CDKL5 Disorder Database) (PP4). The c.146-1G>A variant in CDKL5 has been reported in at least 2 de novo occurrences (biological parentage unconfirmed) in individuals with CDKL5 disorder (internal database - International CDKL5 Disorder Database) (PM6_strong). In summary, the c.146-1G>A variant in CDKL5 is classified as pathogenic for CDKL5 disorder based on the ACMG/AMP criteria (PM2_supporting, PVS1, PP4, PM6_strong).
Met criteria codes
PP4
The c.146-1G>A variant in CDKL5 has been reported in an individual with a clinical phenotype suggestive of CDKL5 disorder (internal database - International CDKL5 Disorder Database) (PP4).
PM2_Supporting
The c.146-1G>A variant in CDKL5 (NM_001323289.2) is absent from gnomAD v2.1.1 (PM2_supporting).
PM6_Strong
The c.146-1G>A variant in CDKL5 has been reported in at least 2 de novo occurrences (biological parentage unconfirmed) in individuals with CDKL5 disorder (internal database - International CDKL5 Disorder Database) (PM6_strong).
PVS1
The c.146-1G>A variant in CDKL5 is predicted to affect a canonical splice site and lead to a truncated or absent protein in a CDKL5 where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1).
Curation History
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