owencqueen/cgbench_data huggingface dataset:
Gene: MECP2 (HGNC:6990)
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.E472, for any frameshift variant that results in a read-through of the stop codon, for canonical splice site variants predicted to result in an out-offrame product, and for canonical splice site variants or single in-frame deletions predicted to preserve the reading frame (exon 3). PVS1 is not applicable for initiation codons
Gene: MECP2 (HGNC:6990)
Evidence Code: PS2 — Very Strong
Modification Type: None
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: MECP2 (HGNC:6990)
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: MECP2 (HGNC:6990)
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 approved functional studies.
Gene: MECP2 (HGNC:6990)
Evidence Code: PM1 — Moderate
Modification Type: Disease-specific
Located in a mutational hot spot and/or critical and well-established functional domain.




Methyl-DNA binding (MBD): aa 90-162


Transcirptional repression domain (TRD): aa 302-306
Gene: MECP2 (HGNC:6990)
Evidence Code: PM4 — Strong
Modification Type: Disease-specific
Protein length changes due to stop-loss variants.




PM4_Strong is applicable to stop-loss variants in 
MECP2
, as several stop loss variants in this gene has been described in affected individuals.
2
Gene: MECP2 (HGNC:6990)
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 PM4 for in-frame deletions/insertions in the Proline-rich region of gene (p.381-p.405)
Gene: MECP2 (HGNC:6990)
Evidence Code: PM5 — Strong
Modification Type: Strength
Missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before.




≥2 different missense changes affecting the amino acid residue.


Do not apply PM1 in these situations.
Gene: MECP2 (HGNC:6990)
Evidence Code: PM5 — Moderate
Modification Type: None
Missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before.




A Grantham or BLOSUM score comparison can be used to determine if the variant is predicted to be as or more damaging than the established pathogenic variant.
Gene: MECP2 (HGNC:6990)
Evidence Code: PM6 — Very Strong
Modification Type: Strength
Confirmed de novo without confirmation of paternity and maternity.




≥4 independent occurrences of PM6. 


Evidence from literature must be fully evaluated to support independent events.
Gene: MECP2 (HGNC:6990)
Evidence Code: PM6 — Moderate
Modification Type: None
Confirmed de novo without confirmation of paternity and maternity.




1 occurrence of PM6.
Gene: MECP2 (HGNC:6990)
Evidence Code: PP1 — Strong
Modification Type: Strength
Co-segregation with disease in multiple affected family members.




≥5 informative meiosis
Gene: MECP2 (HGNC:6990)
Evidence Code: PP1 — Moderate
Modification Type: Strength
Co-segregation with disease in multiple affected family members.




3-4 informative meiosis
Gene: MECP2 (HGNC:6990)
Evidence Code: PP1 — Supporting
Modification Type: Strength
Co-segregation with disease in multiple affected family members.




2 informative meiosis
Gene: MECP2 (HGNC:6990)
Evidence Code: BA1 — Stand Alone
Modification Type: Disease-specific
Use large population databases (i.e. gnomAD).


Use if variant is present at ≥0.0003 (0.03%) in any sub-population.


Use if allele frequency is met in any general continental population dataset of at least 2,000 observed alleles.
Gene: MECP2 (HGNC:6990)
Evidence Code: BS1 — Strong
Modification Type: Disease-specific
Use large population databases (i.e. gnomAD).


Use if variant is present at ≥0.00008 (0.008%) and <0.0003 (0.03%) in any sub-population.


Use if allele frequency is met in any general continental population dataset of at least 2,000 observed alleles.
Gene: MECP2 (HGNC:6990)
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: MECP2 (HGNC:6990)
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: MECP2 (HGNC:6990)
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: MECP2 (HGNC:6990)
Evidence Code: BS4 — Supporting
Modification Type: Strength
Lack of segregation in affected members of a family.




Absent in a similarly affected family member
Gene: MECP2 (HGNC:6990)
Evidence Code: BP2 — Supporting
Modification Type: Disease-specific
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder.
Gene: MECP2 (HGNC:6990)
Evidence Code: BP5 — Supporting
Modification Type: Disease-specific
Variant found in a case with an alternate molecular basis for disease.