The Value of Knowledge and the Cost of False Reassurance: Understanding the Updates to 23andMe’s BRCA Genetic Testing

Silhouettes of 44 people encircle the text, “Updated 23andMe test still misses moist people with BRCA1/2 hereditary cancer risks”. About 1 in 4 of the people are colored in red and the rest are colored in pink. The pink silhouette is intended to represent people who carry a BRCA1 or BRCA2 pathogenic variant that would be missed by the 23andMe test.

What are the BRCA Genes?

The BRCA1 and BRCA2 genes play an important role in helping to protect against developing certain types of cancers by repairing damage that can accumulate in our DNA over time and lead to cancer. Typically, we have two copies of both the BRCA1 and BRCA2 genes (one inherited from each parent).  People who have BRCA-associated hereditary cancer risks have a pathogenic variant (a typo in the DNA code) in one BRCA1/2 gene copy, or that prevents the gene from working properly. As a result, people who carry a pathogenic variant in these genes  have a higher risk of developing certain types of cancers, especially breast, ovarian, prostate, and pancreatic cancer.   

23andMe BRCA Gene Test Updates

The genetic testing company, 23AndMe, was recently given FDA authorization to expand on their Direct-to-Consumer genetic testing that includes analysis of the BRCA1 and BRCA2 genes. The initial version of 23andMe’s BRCA1 and BRCA2 gene analysis evaluated only three specific variants in these genes that are the most common cancer risk-increasing (or “pathogenic”) variants in people of Ashkenazi Jewish ancestry. These three specific variants (BRCA1 c.68_69delAG (185delAG), BRCA1 c.5266dupC (5382insC), and BRCA2 c.5946delT (6174delT)), account for more than 90% of pathogenic variants identified in individuals of Ashkenazi Jewish ancestry.  

This meant that if you carry a harmful mutation in the BRCA1 or BRCA2 genes and  are of 100% Ashkenazi descent, the initial 23andMe test would have quite likely identified your specific variant. However, if you are not of Ashkenazi Jewish ancestry, or have a less common variant,  it is VERY unlikely that your specific variant would have been detected and reported by the 23andMe test.  

The recent update to 23andMe’s DTC test in September 2023 expanded their BRCA1/2 analysis to detect a total of 44 specific variants, including those evaluated previously1. This certainly will increase the detection of genetic variants in the BRCA1 and BRCA2 genes for individuals beyond those who are of Ashkenazi Jewish ancestry. However, given that there are thousands of genetic variants in these two genes that are associated with hereditary cancer risks, it is important to recognize that the updated 23andMe test will still miss the majority of people with BRCA-associated hereditary cancer risks.  

Our review of data  from patients seen in 2023 at Genetic Support Foundation with positive BRCA1/2 test results notes that about 1 in 4 variants in the BRCA1 and BRCA2 genes would have been detected by the 23andMe test.  This means that approximately 75% of variants from the patients we met with would have been missed by the 23andMe test.  

You may have noticed more 23andMe commercials recently with testimonial videos about the power of their current BRCA1/2 testing. Their recent  testing update, coupled with their advertising strategies, will certainly lead to more people receiving positive genetic test results at home rather than in a clinical setting with the guidance and support of medical professionals. Given the expanded but still relatively limited number of variants included, we are concerned that this will also increase the number of people who are falsely reassured by a negative result, who may in fact have a pathogenic variant that runs in their family not assessed by this test.  

Not all BRCA Genetic Tests are the Same

Many people, including some healthcare providers, do not realize that genetic testing through 23andMe does not provide comprehensive analysis of the BRCA1 and BRCA2 genes that is clinically recommended for assessment of hereditary cancer risks. Comprehensive tests read through the entirety of both the BRCA1 and BRCA2  genes, and are much more extensive than a test that simply looks at only a selection of specific variants.

We have met with many patients over the years who sought out 23andMe testing because their personal and/or family history was concerning for a hereditary cancer risk and they believed that the 23andMe test could provide answers for their family. Unfortunately, many have been falsely reassured that they did not carry a BRCA1/2 mutation only to learn later, through a more comprehensive clinical test, that they do indeed carry a variant in one of these genes that the 23andMe test cannot detect and did not report. The offer of this clinical test may only come after the individual or a family member develops a new cancer, bringing this concern to the forefront and prompting clinical testing.   

The Types of Questions We’ve Been Asked About 23andMe’s BRCA Test:

These questions come up often in meetings with patients, friends, and family members. 

Does my 23andMe testing  mean I had complete BRCA1/2 gene analysis?

Comprehensive genetic analysis for all currently known pathogenic variants in the BRCA1/BRCA2 genes includes full gene sequencing and deletion/duplication analysis, neither of which is/was performed with the initial or current version of the 23andMe test. Most people who carry a pathogenic variant in one of these genes will have a normal/negative test result through 23andMe.  

What does it mean if my 23andMe results are positive?

If your results are positive, we recommend confirming these results with a clinical test. In most cases, a pathogenic variant that is detected on 23andMe’s health report will be confirmed through clinical testing. However, per the recommendations included with the 23andMe test, “Results should be confirmed by an independent genetic test prescribed by your own healthcare provider before taking any medical action.”

What does it mean if my 23andMe results are negative?

You may still benefit from additional genetic testing that includes more comprehensive analysis of the BRCA1 and BRCA2 genes and possibly also analysis of other cancer susceptibility genes. While pathogenic variants in the BRCA1 and BRCA2 genes are the most common cause of hereditary breast and ovarian cancer, there are many other genes associated with these cancer types that may be responsible for your personal and/or family history. Even if your genetic testing results are all negative, your healthcare provider may still recommend additional cancer screening and surveillance based on your personal/family history of cancer. This can be reviewed with your doctor or other healthcare providers. 

What do my 23andMe results mean for my family members?

If your results are positive, and confirmed through clinical-grade laboratory testing, any family members who are interested can consider genetic testing for the detected variant to help inform their own cancer screening and risk-reducing practices. A genetic counselor can meet with you and your family members to discuss BRCA-associated cancer risks, genetic inheritance, screening and management recommendations, and benefits and limitations of genetic testing.

If your 23andMe test results are negative, you and other family members may still benefit from  comprehensive genetic testing. A genetic counselor can meet with you and your family to assess the family’s history of cancer, discuss hereditary cancer risks, explain the benefits and limitations of further genetic testing, and coordinate as appropriate for anyone interested.  

Should I consider additional genetic testing beyond 23andMe? 

Some people may benefit from additional testing through a clinical laboratory to comprehensively assess for the presence of variants in the BRCA1/2 genes and possibly other genes; for example, some may benefit from analysis of other genes related to hereditary cancer susceptibility or other genetic health risks outside of cancer. Some people may not find this testing helpful. The importance of further genetic testing may depend on many factors including your personal health and family history. 

Meeting with a genetic counselor can help to clarify the limitations of 23andMe testing and help support you to make an informed decision about your next genetic testing steps. You can request a telehealth appointment with an independent, board certified genetic counselor at Genetic Support Foundation here, or find a genetic counselor in your local community here.  


1As of the date of this posting, 23andMe’s “Health+Ancestry Service” and “23andMe+ Premium”  include analysis of the following 44 variants in the BRCA1 and BRCA2 genes:

BRCA1: c.68_69del, c.213-11T>G, c.427G>T, c.815_824dup, c.1556del, c.1687C>T, c.1960A>T, c.1961del, c.2681_2682del, c.2864C>A, c.3481_3491del, c.3598C>T, c.3627dup, c.3756_3759del, c.3770_3771del, c.4035del, c.4065_4068del, c.4327C>T, c.4357+1G>A, c.4964_4982del, c.4986+6T>G, c.5123C>A, c.5177_5180del, c.5266dup.
BRCA2: c.658_659del, c.771_775del, c.1929del, c.2808_2811del, c.2957_2958insG, c.3170_3174del, c.3264dup, c.3545_3546del, c.3847_3848del, c.4471_4474del, c.5542del, c.5576_5579del, c.5682C>G, c.5946del, c.6037A>T, c.6275_6276del, c.7024C>T, c.7480C>T, c.7934del, c.8904del.