Table 4:

Classification of Novel BRCA2 Variants According to the ACMG guidelines

Variant	Cell viability assay/sensitivity to DNA damaging agents	Classification (evidence)
c.1600G>A (E534K)	Neutral/Neutral	Likely benign (BS1, BP4, BS3)
c.3782C>G (S1261C)	Neutral/Neutral	Likely benign (BP4, BS3)
c.6322C>T (R2108C)	Neutral/Neutral	Likely benign (BS1, BP4, BS3)
c.6929C>A (T2310N)	Neutral/Neutral	Likely benign (BS1, BS3)
c.8356G>A (A2786T)	Neutral/Neutral	Likely benign (BS1, BS3)
c.8393C>T (P2798L)	Neutral/Neutral	Likely benign (BP2, PP3, BS3)
c.9104A>G (Y3035C)	Neutral/Neutral	Likely benign (BS1, PP3, BS3)
c.9104A>T (Y3035F)	Neutral/Neutral	Likely benign (BP4, BS3)
c.9104A>C (Y3035S)	Neutral/Neutral	Uncertain (PP3, BS3, PP1)
c.9106C>G (Q3036E)	Neutral/Neutral	Likely benign (BS3, BP2)
c.9344A>G (K3115R)	Neutral/Neutral	Likely benign (BS1, BS3, BP4)
c.9538C>T (L3180F)	Neutral/Neutral	Likely benign (BS1, BS3)
c.9907A>T S3303C)	Neutral/Neutral	Likely benign (BP4, BS3)
c.68-7T>A (IVS2-7T>A)	Neutral/Neutral	Likely benign (BS1, BS3, BP6)
c.632-10dupT (IVS7-10insT)	Neutral/Neutral	VUS (BS3)
c.8954-5_8954-2delAACA (IVS22-5delAACA)	Neutral/Neutral	Likely benign (BS1, BS3)

Description of ACMG codes (Richards et al., 2015):

BS1:frequency is greater than expected for disorder

BS3:Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing

BP4:Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)

BP2: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

BP6:Reputable source recently reports variant as benign

PP3:Multiple lines of computational evidence support a deleterious effect on the gene or gene product

PP1:Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease