Table 3.

Summary of rare BARD1 missense variants identified in the 1946 patients.

DNA level	Protein effect	Our cohort frequency	gnomAD frequencya	CSVS frequencyb	ClinVarc	Franklind	Finale
c.33G > T	p.Gln11His	0.00513874	0.001634	0.00383693	Benign/Likely benign	Benign	Benign
c.281A > C	p.Asp94Ala	0.00102774	0.00003185	Not present	VUS	VUS	VUS
c.716 T > A	p.Leu239Gln	0.00102774	0.00009244	0.00047801	Likely benign/VUS	VUS	VUS
c.1028C > T	p.Thr343Ile	0.00102774	0.0001168	0.00191479	Benign/VUS	VUS	VUS
c.1318G > A	p.Asp440Asn	0.00051387	0.00000398	Not present	VUS	VUS	VUS
c.1339C > G	p.Leu447Val	0.00051387	0.00007561	Not present	VUS	VUS	VUS
c.1718 T > C	p.Ile573Thr	0.00051387	0.00002476	Not present	VUS	VUS	VUS
c.1835A > T	p.Asp612Val	0.00205549	0.00007434	0.00191479	Likely benign/VUS	VUS	VUS
c.2146A > G	p.Thr716Ala	0.00051387	0.00000795	Not present	VUS	VUS	VUS
c.2161G > A	p.Ala721Thr	0.00051387	0.00002830	Not present	VUS	VUS	VUS
c.2282G > A	p.Ser761Asn	0.00051387	0.001713	0.00047801	Benign/Likely benign/VUS	Benign	VUS

VUS Variant of uncertain significance.

^aTotal allele frequency for all populations described in gnomAD (https://gnomad.broadinstitute.org/).

^bCSVS = Collaborative Spanish Variant Server. Here we show the frequency of the variants found in a local series of 2094 Spanish unrelated individuals that can be considered as controls.

^cAggregate clinical significance from all records at ClinVar (https://ncbi.nlm.nih.gov/clinvar/).

^dClinical classification using ACMG criteria generated by the advanced artificial intelligence Franklin by Genoox (https://franklin.genoox.com/clinical-db/home).

^eFinal classification with our own criteria based on previous information and following ACGM guidelines.