Evaluation of unclassified variants in the breast cancer susceptibility genes BRCA1 and BRCA2 using five methods: results from a population-based study of young breast cancer patients

Table 2 Joint distribution of BRCA1/BRCA2 variants (unclassified variants) according to classification using allele frequency, Polyphen, and sequence conservation

Gene	Classification method	Level	Conservation			Frequency
			Low	Moderate	High	HFUV	LFUV
BRCA1	Frequency	Low risk (HFUV)	3	1	1
		High risk (LFUV)	11	13	15
		P value^a			0.26
	Polyphen	Benign missense	12	10	6	4	24
		Possible damaging	2	3	4	1	8
		Probably damaging	0	1	6	0	7
		P value^a			0.002		0.39
BRCA2	Frequency	Low risk (HFUV)	10	6	2
		High risk (LFUV)	23	23	31
		P value^a			0.018
	Polyphen	Benign missense	26	11	7	11	33
		Possible damaging	5	10	10	5	20
		Probably damaging	2	8	16	2	24
		P value^a			<0.001		0.089

LFUV, low-frequency unclassified variant; HFUV, high-frequency unclassified variant. ^aBased on the exact Mantel–Haenszel chi-square test.

ISSN: 1465-542X