Table 4.

Summary of functional analysis of BRCA2 variants

Variant	Align-GVGD			Protein structure predictiona	Full-length protein detected	Viable Brca2ko/ko ES cells	Sensitivity to DNA-damaging agents	Effect on HR	Effect on splicing	Pathogenicity
	GV	GD	Grade
G25R	0.0	125.1	C65	Unknown	Yes	Yes	Sensitive	50% reduction	None	Likely pathogenic
W31R	0.0	101.3	C65	Disruptiveb	Yes	No	N/A	N/A	Skipping of exon 3	Pathogenic
W31C	0.0	214.4	C65	Disruptiveb	Yes	No	N/A	N/A	None	Pathogenic
P655R	353.9	0.0	C0	Unknown	Yes	Yes	No	No	None	Not pathogenic
R2108H	353.9	0.0	C0	Unknown	Yes	Yes	No	No	None	Not pathogenic
F2406L	112.6	4.9	C0	Unknown	Yes	Yes	No	No	None	Not pathogenic
L2653P	0.0	97.8	C65	Disruptive	Yes	Yes, but reduced	Hypersensitive	90% reduction	None	Likely pathogenic
S2695L	174.6	4.9	C0	No crystal density	Yes	Yes	No	No	None	Not pathogenic
I2944F	4.9	21.3	C0	No effect	Yes	Yes	No	No	None	Not pathogenic
E3002K	0.0	56.87	C55	Disruptive	Yes	No	N/A	N/A	None	Pathogenic
D3095E	0.0	44.6	C65	Disruptive	Yes	No	N/A	N/A	None	Pathogenic
N3124I	0.0	148.9	C65	Disruptive	Yes	No	N/A	N/A	None	Pathogenic

^aBased on Yang et al. (27).

^bBased on Oliver et al. (46).