VIP Variant in BRCA1
The BRCA1 5382insC (5385insC) mutation is estimated to have arisen about 760 years ago [Article:8571953]. This mutation is one of the most common mutations identified among Ashkenazi Jewish families with a history of breast and/or ovarian cancer. The frequency of the mutation in the general Ashkenazi population, unselected for personal or family history of breast or ovarian cancer, is 0.25% or less (see table below).
| Ashkenazi Population | Number of Individuals Tested | Number of Individuals with 5382insC* | Percent | PubMed ID |
|---|---|---|---|---|
| Israel | 399 | 0 | 0.00 | [Article:8841191] |
| U.S./Israel | 433 | 0 | 0.00 | [Article:7550349] |
| United States | 2717 | 4 | 0.15 | [Article:8841191] |
| Australia | 1200 | 3 | 0.25 | [Article:11466700] |
| Total | 4749 | 7 | 0.15 |
*These individuals may be heterozygotic or homozygotic for the 5382insC allele.
In high-risk Ashkenazi families with a history of breast and/or ovarian cancer, the frequency of the 5382insC mutation is significantly higher than in the general Ashkenazi population. In studies of high-risk families with breast and/or ovarian cancer, the percentage of Ashkenazi individuals with 5382insC mutations ranged from 6.5% to 9% [Articles:9042929, 9333265]. In another study, 9% of high-risk Jewish families with breast and/or ovarian cancer were found to harbor the 5382insC mutation, while this mutation was detected in 16% of the subset of families with both breast and ovarian cancer [Article:8898735].
The incidence of the 5382insC mutation in general or non-Jewish populations at high-risk for breast and/or ovarian cancer appears to be lower than that seen for the Ashkenazi population, in the range of 1-4% [Articles:9150149, 7837387, 8533757, 11896095, 7611277]. However, one report indicated 13% of high-risk families studied possessed the 5382insC mutation [Article:7894492].
Note that this variant is referred to in the literature as both 5382insC and 5385insC. The naming confusion is a result of the fact that the sequence from nucleotides 5383-5385 is 'CCC', so that it is impossible to tell at precisely which location the additional C is being inserted.
Please Note: The BRCA1 gene is found on the minus chromosomal strand. Please note that for standardization, the PharmGKB presents all allele base pairs on the positive chromosomal strand, therefore the alleles within our variant annotations will differ (in a complementary manner) from those in this VIP summary that are given on the minus strand as reported in the literature.
| Key Publications: | |
|---|---|
| Diseases | Breast Neoplasms 1 2 3 4 5 6 7 8 9 10 Ovarian Neoplasms 11 12 13 14 15 16 17 18 19 20 |
Appendix
Genomic Variant & GenBank ID: 38462606 C > CC on NC_000017.9
HGVS Nomenclature: NC_000017.9:g.38462606dupC
mRNA Variant & GenBank ID: 5385 C > CC on U14680
HGVS Nomenclature: U14680:r.5385dupC
Protein Variant & GenBank ID: This insertion causes a frameshift that results in premature termination of the protein at codon 1829 [Article:7894492].
GoldenPath Position: Chr17: 38462606 (hg18)
DNA Source Containing Homozygous Minor Allele(Coriell Lines): White (Caucasian): GM13715/NA13715
Key Haplotypes: See BRCA1 Haplotype Information
