Have questions? Visit https://www.reddit.com/r/SNPedia


From SNPedia

BRCA2 is a human tumor suppressor gene. Like most genes, variations in the BRCA2 gene can be either causal for a given disease, or associated with somewhat higher risk, or benign. In clinical terms, a "causal" variation is usually designated as "pathogenic".

However, "causal" (or "pathogenic") does not mean that there is a 100% certainty that a person with such a variant will develop the disease. The clinical synopsis in OMIM for cancers associated with causal BRCA2 mutations is [1]:

  • Mutation carriers have an increased risk of developing breast and/or ovarian cancer at an earlier age
  • Lifetime risk of breast cancer in mutation carriers is 60 to 85%
  • Lifetime risk of ovarian cancer in mutation carriers is 10 to 20%
  • Lifetime risk of breast cancer in male mutation carriers in 6%
  • Increased risk of bilateral breast cancer

There are hundreds of BRCA2 variants that are considered causal/pathogenic, but almost all are very rare (far less than 1% frequency each). [There are also hundreds of other BRCA2 variants that raise one's risk just a bit; these are usually found in 1 - 3% or higher frequencies.] Perhaps the "least rare" causal BRCA2 SNP is:

See also BRCA1 and BRCA2 for an extensive list of breast cancer related SNPs (including variations of all types from benign to causal).

Many other variations of varying consequence are known. These include:

  • rs1799944 (also known as N991D), risk allele G; associated with melanoma
  • rs766173 (also known as N289H), risk allele G
  • rs144848 (also known as N372H or Asn372His), risk allele G
  • rs4987117 (also known as T1915M), risk allele T
  • rs1799954 (also known as R2034C), risk allele T
  • rs11571746 (also known as S2835P), risk allele C
  • rs11571747 (also known as E2856A), risk allele C
  • rs4987047 (also known as I2944F), risk allele T
  • rs11571833 (also known as K3326stop), risk allele T
  • rs1801426 (also known as I3412V), risk allele G
  • rs28897756 (also known as P3039P or 9345G/A), risk allele A. Researchers suggest that a SNP in the BARD1 gene (also called BARD1 Cys557Ser) is an ancient variant that confers risk of single and multiple primary breast cancers, and this risk is amplified in carriers of the BRCA2 999del5 (codon 257, exon 9) mutation, which appears to be this SNP (rs28897756). [PMID 16768547OA-icon.png]

The relative risk of breast cancer associated with PALB2 mutations was estimated to be 2.3 (two-fold). This is similar to the increase in risk seen with the CHEK2, ATM, and BRIP1 genes, reported by the same research group since 2002. PALB2 is the first low-risk gene protein product found that interacts with BRCA2 and all of the other low-risk genes, CHEK2, ATM, and BRIP1, are linked to BRCA1. Together, these genes are thought to account for around 2 percent of all breast cancer cases. [2]

This report from the NCI advises:

  • The cost for genetic testing can range from several hundred to several thousand dollars.
  • Because the results of genetic tests can affect a person's health insurance coverage, some individuals may not want to use their insurance to pay for testing.
  • it can take several weeks or months for test results to become available.

See also BRCA1.