owencqueen/cgbench_data huggingface dataset:
Gene: CDKL5 (HGNC:11411)
Evidence Code: PVS1 — Very Strong
Modification Type: Disease-specific
Null variant in a gene where loss of function is a known mechanism of disease.




Use as defined by ClinGen SVI working group (PMID:30192042).


PVS1 is applicable up to p.R948 
when using the major brain isoform which has an alternative C-terminus (NM_001323289.2)
, for canonical splice site variants predicted to result in an out-of-frame product, for canonical splice site variants or single in-frame deletions predicted to preserve the reading frame (exons 7, 10, 13), and for the non-coding CDKL5 exon (exon 1).
Gene: CDKL5 (HGNC:11411)
Evidence Code: PVS1 — Moderate
Modification Type: Disease-specific
Null variant in a gene where loss of function is a known mechanism of disease.




PVS1_Moderate is applicable for any truncating variant distal of p.R948.(
when using the major brain isoform, NM_001323289.2
) and for canonical splice site variants that flank exon 17 (in-frame exon).
Gene: CDKL5 (HGNC:11411)
Evidence Code: PVS1 — Supporting
Modification Type: Disease-specific
Null variant in a gene where loss of function is a known mechanism of disease.




PVS1_Supporting is applicable for initiation codon variants in 
CDKL5.
Gene: CDKL5 (HGNC:11411)
Evidence Code: PS2 — Very Strong
Modification Type: No change
De novo (maternity and paternity confirmed) in a patient with the disease and no family history.




≥2 independent occurrences of PS2.


≥2 independent occurrences of PM6 and one occurrence of PS2.
Gene: CDKL5 (HGNC:11411)
Evidence Code: PS2 — Strong
Modification Type: None
De novo (maternity and paternity confirmed) in a patient with the disease and no family history.\




1 occurrence of PS2.
Gene: CDKL5 (HGNC:11411)
Evidence Code: PS3 — Supporting
Modification Type: Disease-specific
Well-established in vitro or in vivo functional studies supportive of a damaging effect.




RNA studies that demonstrate abnormal splicing and an inframe product (unless it affects an in-frame exon specified in the PVS1 section).


See included table for acceptable functional studies.
Gene: CDKL5 (HGNC:11411)
Evidence Code: PM1 — Moderate
Modification Type: Disease-specific
Located in a mutational hot spot and/or critical and well-established functional domain.




ATP binding region: aa 19-43; TEY phosphorylation site: aa 169-171
1
,
4
,
2
,
3
Gene: CDKL5 (HGNC:11411)
Evidence Code: PM4 — Moderate
Modification Type: Disease-specific
Protein length changes due to in-frame deletions/insertions in a non-repeat region or stop-loss variants.




Do not use for in-frame deletions/insertions in CDKL5 C-terminus (exons 19-21, or after p.904) (when using the NM_003159.2 transcript).
Gene: CDKL5 (HGNC:11411)
Evidence Code: PM6 — Moderate
Modification Type: None
Confirmed de novo without confirmation of paternity and maternity.




1 occurrence of PM6.
Gene: CDKL5 (HGNC:11411)
Evidence Code: PP1 — Strong
Modification Type: Strength
Co-segregation with disease in multiple affected family members.




≥5 informative meiosis
Gene: CDKL5 (HGNC:11411)
Evidence Code: PP1 — Moderate
Modification Type: Strength
Co-segregation with disease in multiple affected family members.




3-4 informative meiosis
Gene: CDKL5 (HGNC:11411)
Evidence Code: PP1 — Supporting
Modification Type: Strength
Co-segregation with disease in multiple affected family members.




2 informative meiosis
Gene: CDKL5 (HGNC:11411)
Evidence Code: BS2 — Strong
Modification Type: Strength
Observed in the heterozygous/hemizygous state in a healthy adult.




2 unaffected (related or unrelated) heterozygotes or hemizygotes
Gene: CDKL5 (HGNC:11411)
Evidence Code: BS2 — Supporting
Modification Type: Strength
Observed in the heterozygous/hemizygous state in a healthy adult.




1 unaffected (related or unrelated) heterozygote or hemizygote
Gene: CDKL5 (HGNC:11411)
Evidence Code: BS4 — Strong
Modification Type: Strength
Lack of segregation in affected members of a family.




Absent in a similarly affected family member, when seen in two or more families
Gene: CDKL5 (HGNC:11411)
Evidence Code: BS4 — Supporting
Modification Type: Strength
Lack of segregation in affected members of a family.




Absent in a similarly affected family member
Gene: CDKL5 (HGNC:11411)
Evidence Code: BP2 — Supporting
Modification Type: Disease-specific
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder; or observed in cis with a pathogenic variant in any inheritance pattern.




BP2 is not applicable for 
in trans
 state.
Gene: CDKL5 (HGNC:11411)
Evidence Code: BP5 — Supporting
Modification Type: Disease-specific
Variant found in a case with an alternate molecular basis for disease.