. 2021 Oct 28;22(1):9–18. doi: 10.1038/s41397-021-00251-7

Table 2.

Description of the selected 51 genetic variants from 17 candidate DNA-repair genes.

Gene symbol, name, and DNA-repair pathway		Chromosomal location	dbSNP ID	Nucleotide Change	Amino Acid change, or UTR	Functionality Prediction	HapMap (CEU)^a MAF (%)	1000 Genomes (EUR)^b MAF (%)	MAF in this study (%)	HWE p value
ALKBH1	Alkylation Repair Homolog 1, *De-Alkylation pathway*	14q24.3	rs17825440	T>C	Non-syn, M135I	Tolerated	4	2	0	–
ALKBH1	Alkylation Repair Homolog 1, *De-Alkylation pathway*	14q24.3	rs6494	A>T	Non-syn M324L	Tolerated	26	24	16	0.74
APEX1	(APEX nuclease (multifunctional DNA-repair enzyme) 1) *Base Excision Repair Pathway*		rs1760944	T>G	Utr-5¹	No direct binding	43	35	46	0.66
			rs3136814	C>A	Utr-5¹	Tolerated	3	4	4	0.002
			rs3136817	C>T	Intron	No miRNA binding	22	29	19	0.23
			rs1130409	G>T	Non-syn, D148E		46	49	44	0.01
			rs4585	G>T	utr-3¹		47	38	–	–
ATM	Ataxia Telangiectasia Mutated, *Homologous recombination pathway*	11q22–q23	rs592955	A>C	utr-5¹	No direct binding	43	38	49	0.8
			rs609261	T>C	utr-5¹	Possibly damaging	49	38	49	0.9
			rs1801516	T>C	non-syn, D1853N	Tolerated	17	16	8	0.3
BRCA1	Breast Cancer 1, Early Onset, *Homologous recombination pathway*	17q21.31	rs1799966	C>T	Non-syn, S1613C	Damaging	34	35	32	0.38
			rs28897687	C>A	Non-syn, N1236K	Damaging	1.1	0	–	–
			rs4986852	T>C	Non-syn, S1040N	Damaging	5	2	0	–
			rs4986850	T>C	Non-Syn, D693N	Damaging	10	8	4	0.05
EXO1	Exonuclease 1, *Homologous recombination and Mismatch repair pathways*	1q42–q43	rs1776177	C>T	Non-syn,	Not found	49	46	48	0.74
			rs1776179	C>T	Non-syn	Not Found	27	31	27	0.15
			rs735943	A>G	Non-syn, H354R	Tolerated	42	42	34	0.302
			rs4149963	T>C	Non-Syn, T439M	Tolerated	7	8	8	0.004
			rs4149965	A>G	Non-Syn, V458M	Tolerated	30	25	12	0.94
			rs1047840	A>G	Non-syn,	Not found	39	37	43	0.78
			rs1776148	A>G	Non-Syn, E670G	Tolerated	35	34	29	0.401
			rs9350	T>C	Non-Syn, P757L	Damaging	15	15	25	0.186
FAN1	Fanconi-Associated Nuclease 1 *Homologous recombination pathway*	14q11.2	rs6493352	T>C	Non Syn, R648H	Tolerated	17	18	20	0.58
FANCD2	Fanconi Anemia, Complementation Group D2 *Homologous recombination pathway*	3p25.3	rs9845756	T>C	Utr-5¹	Possibly damaging	20	13	0	–
FANCD2		3p25.3	rs3172417	T>C	Utr-3¹		39	45	23	0.17
Lig1	Ligase I, DNA, ATP-Dependent, *Base Excision Repair Pathway*	19q13.33	rs20580	A>G	Utr-5¹	No direct binding	46	49	42	0.72
Lig1		19q13.33	rs3730842	C>T	Coding-syn	Not found	13	10	20	0.56
Lig4	ligase IV, DNA, ATP-dependent, *Base Excision Repair Pathway*	13q33.3	rs1805388	A>G	Missense, T9I	Damaging	19	16	15	0.84
MGMT	O-6-Methylguanine-DNA Methyltransferase,*De-Alkylation pathway*	10q26.3	rs10764881	A>G	Near-gene-5¹	No direct binding	37	30	19	0.61
			rs12917	T>C	Non-syn, L115F	Damaging	10	13	18	0.90
			rs2308321	G>A	Non syn, I174V	Tolerated	16	13	7	0.49
			rs2308327	G>A	Non-syn, K209R	Tolerated	9	13	10	0.34
			rs113813075	C>A	Utr-5¹		5	6
MRE11	Meiotic Recombination 11 Homolog A, *Homologous recombination pathway*	11q21	rs215509	C>T	Utr-3¹		32	12	33	0.67
			rs533984	A>G	Intron		39	40	48	0.03
			rs1805363	T>C	Utr-5¹		9	8	8	0.40
NBN	Nijmegen Breakage Syndrome 1, *Homologous recombination pathway*	8q21.3	rs1805800	T>C	Utr-5¹	Not direct binding	28	30	–	–
			rs1805794	G>C	Non-syn, E185Q	Tolerated	31	30	0	–
			rs2735383	G>C	Utr-3¹		32	29	37	0.06
RAD50	RAD50 homolog, *Homologous recombination pathway*	5q31.1	rs3798135	T>C	Intron		21	19	25	0.30
			rs2522403	C>T	Intron		22	19	31	0.05
			rs10520114	G>A	Intron		22	18	16	0.27
RAD51	RAD51 Recombinase, *Homologous recombination pathway*	15q15.1	rs2619679	T>A	Utr-3		47	49	42	0.23
			rs7180135	G>A	Utr-3	Not found	47	43	27	0.55
			rs1801321	T>G	Non-syn,		47	42	27	0.81
RAD52	RAD52 Homolog *Homologous recombination pathway*	12p13.33	rs7310449	C>T	Utr-3¹		44	42	0	–
			rs7301931	C>T	Utr-3¹		49	43	45	0.40
			rs11571475	G>A	Utr-3¹		13	13	11	0.29
RFC1	Replication factor C, *Mismatch Repair pathway*	4p14-p13	rs6844176	C>T	Intron		38	43	48	0.38
XRCC1	X-Ray Repair Complementing Defective Repair In Chinese Hamster Cells, *Base Excision Repair Pathway*	19q13.2	rs25489	T>C	Missense, R280H	damaging	10	5	3	0.23
			rs1799782	A>G	Missense, R194W	damaging	12	5	12	0.43
			rs25487	T>C	Missense, Q399R	damaging	23	36	26	0.78

^aCEU-Utah residents of Northern and Western European Ancestry.

^bEUR-European population including both Finnish and non-Finnish European subpopulations.

The in silico functional evaluation for the non-synonymous genetic variants were predicted using four different tools SIFT (https://sift.bii.a-star.edu.sg), Polyphen (http://genetics.bwh.harvard.edu/pph2/), SNPs3D (http://www.snps3d.org), and PANTHER (http://www.pantherdb.org). The functional importance of the SNPs within 5′ flanking regions was predicted by looking at potential transcriptional binding sites, which may affect transcription, using the MatInspector tool (www.genomatx.de). The same approach was performed for SNPs within 3′ UTR looking for miRNA sites using TargetScan Human 5.1 (http://www.targetscan).