owencqueen/cgbench_data huggingface dataset:
Gene: CDH1 (HGNC:1748)
Evidence Code: PVS1 — Very Strong
Per ClinGen SVI guidelines with the exception of canonical splice sites.
Gene: CDH1 (HGNC:1748)
Evidence Code: PVS1 — Strong
Per modified CDH1 PVS1 decision tree. Other CDH1 caveats:




Use the strong strength of evidence for canonical splice sites.


CDH1 Exonic deletions or tandem duplications of in-frame exons.


Truncations in NMD-resistant zone located upstream the most 3’ well-characterized pathogenic variant c.2506G>T (p.Glu836*). Use PVS1_moderate if premature stop is downstream of this variant.
Gene: CDH1 (HGNC:1748)
Evidence Code: PVS1 — Moderate
Per modified CDH1 PVS1 decision tree. Other CDH1 caveats:




G to non-G variants disrupting the last nucleotide of an exon.


Canonical splice sites located in exons demonstrated experimentally to result in in-frame partial skipping/insertion (e.g., Exon 3 donor site).
Gene: CDH1 (HGNC:1748)
Evidence Code: PS1 — Strong
Per original ACMG/AMP guidelines.
Gene: CDH1 (HGNC:1748)
Evidence Code: PS2 — Very Strong
≥Two patients with DGC &/or LBC w/ parental confirmation.
Gene: CDH1 (HGNC:1748)
Evidence Code: PS2 — Strong
One patient with DGC &/or LBC w/ parental confirmation.
Gene: CDH1 (HGNC:1748)
Evidence Code: PS3 — Supporting
RNA assay demonstrating abnormal in-frame transcripts.
Gene: CDH1 (HGNC:1748)
Evidence Code: PS4 — Very Strong
Sixteen families meet HDGC criteria.
Gene: CDH1 (HGNC:1748)
Evidence Code: PS4 — Strong
Four families meet HDGC criteria.
Gene: CDH1 (HGNC:1748)
Evidence Code: PS4 — Moderate
Two families meet HDGC criteria.
Gene: CDH1 (HGNC:1748)
Evidence Code: PM2 — Moderate
<One out of 100,000 alleles in gnomAD cohort; if present in >2 individuals, must be present in <One out of 50,000 alleles within a sub-population.
Gene: CDH1 (HGNC:1748)
Evidence Code: PM4 — Moderate
Per original ACMG/AMP guidelines.
Gene: CDH1 (HGNC:1748)
Evidence Code: PM6 — Very Strong
≥Four patients with DGC &/or LBC w/o parental confirmation.
Gene: CDH1 (HGNC:1748)
Evidence Code: PM6 — Strong
≥Two patients with DGC &/or LBC w/o parental confirmation.
Gene: CDH1 (HGNC:1748)
Evidence Code: PM6 — Moderate
One patient with DGC &/or LBC w/o parental confirmation.
Gene: CDH1 (HGNC:1748)
Evidence Code: PP1 — Strong
≥Seven meioses across ≥2 families.
Gene: CDH1 (HGNC:1748)
Evidence Code: PP3 — Supporting
At least three in silico splicing predictors in agreement (.Human Splicing Finder (HSF), Maximum Entropy (MaxEnt), Berkeley Drosophilia Genome Project (BDGP), or ESEfinder).
Gene: CDH1 (HGNC:1748)
Evidence Code: BS2 — Strong
Variant seen in ≥10 individuals w/o DCG, SRC tumors, or LBC & whose families do not suggest HDGC.
Gene: CDH1 (HGNC:1748)
Evidence Code: BS2 — Supporting
Variant seen in ≥3 individuals w/o DCG, SRC tumors, or LBC & whose families do not suggest HDGC.
Gene: CDH1 (HGNC:1748)
Evidence Code: BP2 — Supporting
Variant is observed in cis (or phase is unknown) w/ a pathogenic variant.
Gene: CDH1 (HGNC:1748)
Evidence Code: BP4 — Supporting
Splicing predictions only. At least three in silico splicing predictors in agreement (Human Splicing Finder (HSF), Maximum Entropy (MaxEnt), Berkeley Drosophilia Genome Project (BDGP), or ESEfinder).
Gene: CDH1 (HGNC:1748)
Evidence Code: BP7 — Supporting
Synonymous variants where nucleotide is not highly conserved; variant is the reference nucleotide in one primate and/or >3 mammal species.