Description
This mutation is caused by the deletion of two nucleotides (AG) in BRCA1 exon 2, and is denoted c.68_69delAG at the cDNA level using current HGVS nomenclature, or Glu23ValfsX16 at the protein level. The mutation is also known as BRCA1 185delAG or 187delAG and is a founder mutation in the Ashkenazi Jewish population (Struewing 1995). The deletion causes a frameshift, which changes a Glutamic acid to a Valine at codon 23 and creates a premature stop codon at position 16 of the new reading frame. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay and is indicative of Hereditary Breast and Ovarian Cancer (HBOC) syndrome, an autosomal dominant condition that predisposes to breast and ovarian cancer as well as other cancers. The predominant BRCA1-related cancer risks for women who have not been diagnosed with cancer have been estimated to be 57% - 84% lifetime risk for breast cancer and 24% - 54% lifetime risk for ovarian cancer (Antoniou 2003, Chen 2007, Ford 1998). BRCA1 mutations have also been reported in women with fallopian tube carcinoma, primary peritoneal carcinoma, and uterine serous carcinoma (Levine 2003, Pennington 2013). Women with BRCA1/2 mutations also have an increased risk for contralateral breast cancer. Women with BRCA mutations whose first cancer was diagnosed under age 40 have a 21-31% risk to develop a second breast cancer within 10 years and a 63% risk to develop a second breast cancer within 25 years. Women with BRCA mutations whose first cancer was diagnosed between ages 40 and 50 have an 11-13% risk to develop a second breast cancer within 10 years and a 44-49% risk within 25 years. Women with BRCA mutations whose first cancer was diagnosed after age 50 have an 8% risk to develop a second breast cancer within 10 years and a 20% risk within 25 years (Graeser 2009). Other cancer risks associated with a BRCA1 mutation include approximately 3% risk for pancreatic cancer (The Breast Cancer Linkage Consortium 1999), a 20% risk for prostate cancer (Thompson 2002), and 4% risk for male breast cancer (Liede 2004). The variant is found in BR-OV-HEREDIC,BRCA1-BRCA2,BRCA-AJ,HIRISK-BR-HEREDIC,HEREDICANCER panel(s).
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
