owencqueen/cgbench_data huggingface dataset:
Gene: BRCA2 (HGNC:1101)
Evidence Code: BP4 — Supporting
Modification Type: Clarification,Gene-specific
Missense or in-frame insertion, deletion or delins variants inside a (potentially) clinically important functional domain, and no predicted impact via protein change or splicing (BayesDel no-AF score ≤ 0.18 AND SpliceAI ≤0.1).


Silent variant inside a (potentially) clinically important functional domain, if no predicted impact via splicing (SpliceAI ≤0.1).


Intronic variants outside of the native donor and acceptor splice sites (i.e. not +/- 1,2 positions) AND no predicted impact via splicing (SpliceAI ≤0.1).


As justified in the appendices, (potentially) clinically important functional domains are defined as: BRCA2 PALB2 binding domain aa 10-40; BRCA2 DNA binding aa 2481-3186. See Specifications Figure1A and Appendix J for details.
Gene: BRCA2 (HGNC:1101)
Evidence Code: BP5 — Original ACMG Summary
Variant found in a case with an alternate molecular basis for disease.
Gene: BRCA2 (HGNC:1101)
Evidence Code: BP5 — Strong
Modification Type: Gene-specific
Use ONLY to capture combined LR against pathogenicity, based on multifactorial likelihood clinical data.


BP5_VeryStrong – LR <0.00285:1


BP5_Strong  - LR <0.05:1


Not applicable for co-observation: cases with pathogenic variants in two (or more) different known breast–ovarian cancer risk genes have no specific phenotype.
Gene: BRCA2 (HGNC:1101)
Evidence Code: BP5 — Moderate
Modification Type: Gene-specific
Use ONLY to capture combined LR against pathogenicity, based on multifactorial likelihood clinical data.


BP5_Moderate - LR <0.23:1


Not applicable for co-observation: cases with pathogenic variants in two (or more) different known breast–ovarian cancer risk genes have no specific phenotype.
Gene: BRCA2 (HGNC:1101)
Evidence Code: BP5 — Supporting
Modification Type: Gene-specific
Use ONLY to capture combined LR against pathogenicity, based on multifactorial likelihood clinical data.


BP5 - LR 0.23-0.48:1


Not applicable for co-observation: cases with pathogenic variants in two (or more) different known breast–ovarian cancer risk genes have no specific phenotype.
Gene: BRCA2 (HGNC:1101)
Evidence Code: BP6 — Original ACMG Summary
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
Gene: BRCA2 (HGNC:1101)
Evidence Code: BP7 — Original ACMG Summary
A synonymous variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved.
Gene: BRCA2 (HGNC:1101)
Evidence Code: BP7 — Strong
Modification Type: General recommendation,Gene-specific
Well-established in vitro or in vivo functional studies shows no damaging effect on protein function 
as measured by effect on mRNA transcript profile – mRNA assay only.
 Apply as BP7_Strong (RNA) for intronic and silent variants, as well as missense/in-frame variants located outside a (potentially) clinically important functional domain. See Specifications Figure1B and Appendix E for details.


As justified in the appendices, (potentially) clinically important functional domains are defined as: BRCA2 PALB2 binding domain aa 10-40; BRCA2 DNA binding aa 2481-3186. See Specifications Figure1A and Appendix J for details.
Gene: BRCA2 (HGNC:1101)
Evidence Code: BP7 — Supporting
Modification Type: Clarification,General recommendation
Silent variant inside a (potentially) clinically important functional domain, IF BP4 met.


Intronic variants located outside conserved donor or acceptor motif positions (at or beyond positions +7/-21) IF BP4 met.


See Specifications Figure1A and Appendix J for additional details.


As justified in the appendices, (potentially) clinically important functional domains are defined as: BRCA2 PALB2 binding domain aa 10-40; BRCA2 DNA binding aa 2481-3186. See Specifications Figure1A and Appendix J for details.