Table 2.
Variants of unknown clinical significance identified in established and candidate breast or ovarian cancer genes in a South African Breast cancer cohort of African ancestry.
| Gene (RefSeq)* | Variant | Exon | Predicted protein change | dbSNP | Patient | Age (years:months) |
|---|---|---|---|---|---|---|
| ATM (NM_000051.3) | c.131A > G | Exon 3 | p.Asp44Gly | rs150143957 | BRB146 | 52:2 |
| BRB38 | 46:10 | |||||
| BRB49 | 43:4 | |||||
| ATM | c.320G > A | Exon 4 | p.Cys107Tyr | rs142358238 | BRB171 | 37:4 |
| BRB68 | 43:0 | |||||
| ATM | c.1358C > T | Exon 10 | p.Pro453Leu | rs786204124 | BRB121 | 54:0 |
| BRB170 | 40:2 | |||||
| BRB194 | 44:1 | |||||
| ATM | c.3078G > C# | Exon 21 | p.Trp1026Cys | – | BRB146 | 52:2 |
| ATM | c.4329C > A | Exon 29 | p.His1443Gln | rs377065665 | BRB131 | 45:3 |
| BRB17 | 44:11 | |||||
| BRB229 | 38:11 | |||||
| BRB281 | 51:0 | |||||
| BRB78 | 36:4 | |||||
| ATM | c.6176C > T | Exon 42 | p.Thr2059Ile | rs144761622 | BRB239 | 51:11 |
| BRB241 | 40:1 | |||||
| BRB252 | 40:9 | |||||
| ATM | c.6194T > C | Exon 42 | p.Ile2065Thr | rs372838622 | BRB19 | 36:0 |
| ATM | c.8558C > T | Exon 58 | p.Thr2853Met | rs141534716 | BRB10 | 42:8 |
| BRB162 | 42:10 | |||||
| BRB203 | 39:7 | |||||
| BRB270 | 41:2 | |||||
| BRB73 | 29:11 | |||||
|
BRCA2 |
c.4798_4800del | Exon 11 | p.Asn1600del | rs276174851 | BRB193 | 43:5 |
| BRB268 | 46:2 | |||||
| BRB98 | 43:3 | |||||
| BRCA2 | c.7762A > G# | Exon 16 | p.Ile2588Val | – | BRB158 | 53:7 |
| BRCA2 | c.8390A > G# | Exon 19 | p.Asp2797Gly | – | BRB8 | 28:0 |
| BRCA2 | c.9088A > C# | Exon 23 | p.Thr3030Pro | – | BRB88 | 39:3 |
| BRIP1 (NM_032043.2) | c.2131A > G | Exon 15 | p.Thr711Ala | rs760515227 | BRB207 | 49:9 |
| MSH2 (NM_000251.2) | c.508C > G | Exon 3 | p.Gln170Glu | rs63750843 | BRB106 | 35:0 |
| BRB14 | 47:8 | |||||
| BRB154 | 51:2 | |||||
| BRB238 | 44:10 | |||||
| MSH6 (NM_000179.2) | c.560A > G# | Exon 3 | p.Lys187Arg | – | BRB246 | 42:1 |
| MSH6 | c.2083C > T# | Exon 4 | p.Leu695Phe | – | BRB182 | 41:2 |
| BRB208 | 44:8 | |||||
| BRB284 | 30:10 | |||||
| BRB98 | 43:3 | |||||
| MSH6 | c.2347 T > A | Exon 4 | p.Cys783Ser | rs373721483 | BRB74 | 47:4 |
| MSH6 | c.2962C > T | Exon 4 | p.Arg988Cys | rs61753795 | BRB62 | 43:7 |
| MSH6 | c.3489A > C | exon 6 | p.Glu1163Asp | rs531674673 | BRB239 | 51:11 |
| BRB270 | 41:2 | |||||
| BRB276 | 46:6 | |||||
| BRB51 | 52:6 | |||||
| BRB52 | 46:11 | |||||
| BRC134 | 45:11 | |||||
| NBN (NM_002485.4) | c.706A > G | Exon 7 | p.Lys236Glu | rs1060503482 | BRB89 | 48:8 |
| NF1 (NM_001042492.2) | c.4943C > T | Exon 37 | p.Thr1648Ile | rs376655102 | BRB174 | 37:8 |
| BRB42 | 49:11 | |||||
| PALB2 (NM_024675.3) | c.23C > T | Exon 1 | p.Pro8Leu | rs150390726 | BRB55 | 32:9 |
| BRB89 | 48:8 | |||||
| RAD51C (NM_058216.2) | c.779G > A | Exon 5 | p.Arg260Gln | rs730881926 | BRB197 | 51:0 |
| RAD51D (NM_002878.3) | c.250A > G | Exon 3 | p.Thr84Ala | rs200018296 | BRB111 | 42:7 |
| STK11 (NM_000455.4) | c.888G > C | Exon 7 | p.Lys296Asn | rs1555738868 | BRB199 | 45:2 |
| BRB275 | 47:4 | |||||
| TP53 (NM_000546.5) | c.476C > T | Exon 5 | p.Ala159Val | rs1555526131 | BRB102 | 40:9 |
| TP53 | c.393_395del | Exon 5 | p.Asn131del | rs879254214 | BRB234 | 39:10 |
Variants are named according to the Human Genome Variation Society (HGVS) nomenclature, where complimentary DNA (cDNA) numbering + 1 corresponds to the A of the ATG translation initiation codon.
*Reference sequences obtained from the NCBI database. For BRCA1 the most common human transcript (NM_007294.3) is used with custom numbering of the exons (missing exon 4).
#Not reported in dbSNP (http://www.ncbi.nlm.nih.gov/SNP), EVS (http://evs.gs.washington.edu/EVS), gnomAD (https://gnomad.broadinstitute.org) or ClinVar (https://www.ncbi.nlm.nih.gov/clinvar).