Conditions tested for—and other key details to know.

AncestryHealth® now uses next-generation sequencing technology (NGS) to detect variants in genes linked to certain inherited health conditions. Before July 31, 2020, AncestryHealth used microarray technology. As you may know, because the variants each test can detect is different, it is important you know which technology was used to analyze your patient’s DNA. This information can be found in their laboratory report.

The tables below outline the health conditions, genes, and either percent of known variants that can be detected (NGS) or the specific variants the test looks for (microarray). NGS only looks for specific variants where noted (F2, F5, HBB, HFE genes).

Next-Generation Sequencing (NGS)

Kits purchased after July 31st 2020. Estimated percentage of variants detected for each gene.

Cancer Risk Panel

- Gene Included: ATM
- Variants Detected: ~90%
- People with certain DNA variants in their ATM gene have a higher chance of developing certain cancers, especially breast cancer in women.
- Genes Included: BRCA1, BRCA2
- Variants Detected: ~80%
- People with HBOC syndrome have a DNA variant in the BRCA1 or BRCA2 genes that increase the chances of developing breast cancer and ovarian cancer (in women) or breast cancer and prostate cancer (in men), often at an earlier age.
- Gene Included: PALB2
- Variants Detected: >80%
- Both men and women with certain DNA variants in their PALB2 gene have a higher chance of developing breast cancer and certain other cancers including pancreatic cancer.
- Gene Included: APC
- Variants Detected: 90%
- Certain DNA variants in the APC gene are linked to the inherited conditions familial adenomatous polyposis (FAP) and attenuated FAP (AFAP). People with FAP have hundreds to thousands of colon polyps and a nearly 100% chance of developing colon cancer in their lifetime. People with AFAP develop fewer polyps than people with FAP and have up to a 70% chance of developing colon cancer in their lifetime.
- Gene Included: BMPR1A
- Variants Detected: 69%-89%
- Juvenile polyposis syndrome (JPS) is due to DNA variants in the BMPR1A or SMAD4 gene. People with JPS can have a significantly higher chance of developing colon cancer in their lifetime.
- Genes Included: MLH1, MSH2, MSH6, PMS2
- Variants Detected: ~80%
- People with Lynch syndrome have an increased chance of developing colon, uterine, and several other cancers, often at an earlier age.
- Gene Included: MUTYH
- Variants Detected: >90%
- MAP is a genetic condition that significantly increases the chance of developing colon cancer and several other cancers, such as duodenal cancer and, in women, ovarian cancer. People can either be a carrier of MAP or have MAP. Carriers of MAP do not have the condition but if they have children with someone who is also a carrier or has MAP, their children might. Carriers also have a slightly increased chance of developing colon cancer.
- Gene Included: POLD1
- Variants Detected: ~80%
- Certain DNA variants in the POLD1 gene are linked to a higher chance of developing colon and possibly other cancers.
- Gene Included: POLE
- Variants Detected: ~80%
- Certain DNA variants in the POLE gene are linked to a higher chance of developing colon and possibly other cancers.
- Gene Included: SMAD4
- Variants Detected: >80%
- Juvenile polyposis syndrome (JPS) is due to a DNA variant in the BMPR1A or SMAD4 gene. People with JPS can have a significantly higher chance of developing colon cancer in their lifetime. Many people with a DNA variant in SMAD4 also have a condition called hereditary hemorrhagic telangiectasia (HHT). HHT causes problems with the blood vessels, which can lead to health issues such as excessive nosebleeds and other abnormal bleeding events.
- Gene Included: CHEK2
- Variants Detected: >80%
- People with certain DNA variants in their CHEK2 gene have a higher chance of developing certain cancers, especially colon, breast (especially in women but men may have an increased risk too), and prostate cancer (in men).
- Gene Included: STK11
- Variants Detected: >80%
- PJS is a genetic condition that increases the chance of developing colon cancer, breast cancer (in women), and other types of cancer, such as cancer of the pancreas, stomach, and small bowel. Most people with PJS have a DNA variant identified in the STK11 gene.

Heart and Blood Health

- Genes Included: MYBPC3, MYH7
- Variants Detected: >80%
- Cardiomyopathy is a disease of the heart muscle that can lead to problems ranging from an irregular heartbeat to heart failure. Other genes not included in this test are also associated with cardiomyopathy.
- Genes Included: APOB, LDLR, PCSK9
- Variants Detected: >90%
- People with familial hypercholesterolemia have a higher chance than typical of developing very high levels of LDL cholesterol, which can increase the chance of a heart attack.
- Gene Included: HFE
- Variants Detected: >90%
- Hereditary hemochromatosis can lead to having too much iron in the blood. People with hereditary hemochromatosis can sometimes develop iron overload disorder, which happens when too much iron builds up in the body. Left untreated, elevated iron levels can lead to permanent organ damage.
- Note: this test detects the following two variants that account for 90% of the cases of type 1 hereditary hemochromatosis:
  - NM_000410.3(HFE):c.187C>G (p.His63Asp)
  - NM_000410.3(HFE):c.845G>A (p.Cys282Tyr)
- Genes Included: F2, F5
- Variants Detected: >90%
- Hereditary thrombophilia can increase the chances of developing potentially dangerous blood clots. People with hereditary thrombophilia have a higher chance of developing blood clots inside veins when they shouldn’t. This can lead to health problems and, in some cases, be life–threatening.
- Note: this test detects the following two variants that account for the majority of the cases of hereditary thrombophilia
  - NM_000506.4(F2):c.*97G>A
  - NM_000130.4(F5):c.1601G>A (p.Arg534Gln)

Carrier Status

- Gene Included: CFTR
- Variants Detected: >90%
- Cystic Fibrosis (CF) carriers do not have CF but their children might. CF is an inherited condition that leads to a buildup of thick, sticky mucus that damages the lungs, pancreas, and other organs. This causes difficulty breathing and other potentially serious problems. If both biological parents are carriers of CF, then each of their children has a 1 in 4 chance of developing CF. Knowing whether they are a carrier of CF is especially important for people who are planning on having children.
- Gene Included: HBB
- Variants Detected: >90%
- Sickle cell anemia carriers do not have sickle cell anemia but their children might. Sickle cell anemia is an inherited disease that affects red blood cells, which carry oxygen throughout the body. The disease causes red blood cells to change shape and no longer work well. That can lead to severe pain, vision problems, organ damage, stroke, and a shorter lifespan. If both biological parents are carriers of sickle cell anemia, then each of their children has a 1 in 4 chance of developing the condition. Knowing whether they are a carrier of sickle cell anemia is especially important for people who are planning on having children.
- Note: this test detects the single variant that is linked to sickle cell anemia:
  - NM_000518.5(HBB):c.20A>T (p.Glu7Val)
- Gene Included: HEXA
- Variants Detected: >90%
- Tay-Sachs carriers do not have Tay-Sachs disease but their children might. Tay-Sachs disease is an inherited condition that leads to the deterioration of cells in the brain and spinal cord, typically leading to muscle weakness and death in early childhood. If both biological parents are carriers of Tay-Sachs disease, then each of their children has a 1 in 4 chance of developing the disease. Knowing whether they are a carrier of Tay-Sachs disease is especially important for people who are planning on having children.

Connective Tissue Disorders

- Genes Included: COL5A1, COL5A2
- Variants Detected: >90%
- Classical EDS typically causes issues with the skin and joints. This leads to skin that is softer and more stretchy than normal, wounds that take longer to heal, scars that are more visible than typical, and a higher chance of joint pain and dislocation. Serious problems with the heart or blood vessels can happen but are thought to be less common in people with classical EDS than in people with some other connective tissue disorders.
- Gene Included: ACTA2
- Variants Detected: >90%
- FTAAD primarily affects the connective tissues in the thoracic aorta. The thoracic aorta is the upper part of the blood vessel that carries blood from your heart to the rest of your body. It can lead to a higher chance of an aneurysm and/or dissection in this blood vessel. Somewhere between 12-20% of FTAAD cases are explained by known variants in the gene this test analyzes.
- Genes Included: TGFBR1, TGFBR2, TGFB2, TGFB3
- Variants Detected: >90%
- LDS affects the connective tissues in the blood vessels, bones, and skin. This can lead to a higher chance of an aneurysm and/or dissection in the aorta and other major arteries. LDS can also lead to asthma, eye problems, scoliosis, a cleft palate, and other issues. More than 80% of LDS cases are explained by known variants in the four genes this test analyzes.
- Gene Included: FBN1
- Variants Detected: >90%
- Marfan syndrome can cause issues with the heart, blood vessels, eyes, bones, and lungs. Most people with Marfan syndrome will develop an aneurysm and/or dissection at some point in their lives. They may also develop eye problems, heart problems, scoliosis, or a sunken or protruding chest.
- Gene Included: COL3A1
- Variants Detected: >90%
- Vascular EDS affects the connective tissues in the blood vessels and organs by making the walls of these body parts more fragile than typical. People with vascular EDS have a high chance of developing an aneurysm, dissection, or rupture. These problems can happen anywhere along the aorta as well as in major blood vessels in the head, neck, arms, and legs. Vascular EDS can also lead to ruptures in other organs, including the uterus in pregnant women.

The variants we test for are carefully selected.

Based on expert recommendations, only variants known to be linked to a higher chance of developing certain health issues are reported. An analysis of the variants is made by the lab that performed the test.

Why specific variants are not listed for NGS.

Standard microarray technology typically tests so few DNA variants linked to certain health conditions that it’s important to have a list of exactly which variants were tested. In comparison, NGS can detect so many DNA variants that it’s typically more useful to know the percentage of known variants that can be detected in each gene, as well as the types of variants it cannot detect—such as large duplications or deletions.

Microarray

Kits purchased before August 1st 2020. List of specific gene variants for each condition tested.

Cancer Risk

People with HBOC syndrome have a DNA variant in the BRCA1 or BRCA2 genes that increase the chances of developing breast cancer and ovarian cancer (in women) or breast cancer and prostate cancer (in men), often at an earlier age.

Variants detected by microarray technology
BRCA1
- NM_007294.3(BRCA1):c.5277+1delG
- NM_007294.3(BRCA1):c.181T>G (p.Cys61Gly)
- NM_007294.3(BRCA1):c.4964_4979delCTGGCCTGACCCCAGA (p.Ser1655Terfs)
- NM_007294.3(BRCA1):c.5503C>T (p.Arg1835Ter)
- NM_007294.3(BRCA1):c.2035A>T (p.Lys679Ter)
- NM_007294.3(BRCA1):c.3331C>T (p.Gln1111Ter)
- NM_007294.3(BRCA1):c.2138C>G (p.Ser713Ter)
- NM_007294.3(BRCA1):c.4964C>T (p.Ser1655Phe)
- NM_007294.3(BRCA1):c.1556delA (p.Lys519Argfs)
- NM_007294.3(BRCA1):c.2457delC (p.Asp821Ilefs)
- NM_007294.3(BRCA1):c.3331_3334delCAAG (p.Gln1111Asnfs)
- NM_007294.3(BRCA1):c.5266dupC (p.Gln1756Profs)
- NM_007294.3(BRCA1):c.68_69delAG (p.Glu23Valfs)
- NM_007294.3(BRCA1):c.2681_2682delAA (p.Lys894Thrfs)
- NM_007294.3(BRCA1):c.5277+1G>A
- NM_007294.3(BRCA1):c.5277+1G>T
- NM_007294.3(BRCA1):c.4964_4982del19 (p.Ser1655Tyrfs)
- NM_007294.3(BRCA1):c.5503_5564del62 (p.Arg1835Thrfs)
BRCA2
- NM_000059.3(BRCA2):c.8167G>C (p.Asp2723His)
- NM_000059.3(BRCA2):c.2830A>T (p.Lys944Ter)
- NM_000059.3(BRCA2):c.3265C>T (p.Gln1089Ter)
- NM_000059.3(BRCA2):c.5645C>A (p.Ser1882Ter)
- NM_000059.3(BRCA2):c.7878G>C (p.Trp2626Cys)
- NM_000059.3(BRCA2):c.2330dupA (p.Asp777Glufs)
- NM_000059.3(BRCA2):c.3264dupT (p.Gln1089Serfs)
- NM_000059.3(BRCA2):c.3545_3546delTT (p.Phe1182Terfs)
- NM_000059.3(BRCA2):c.5946delT (p.Ser1982Argfs)
People with Lynch syndrome have an increased chance of developing colon, uterine, and several other cancers, often at an earlier age.

Variants detected by microarray technology
MLH1
- NM_000249.3(MLH1):c.1897-2A>G
MSH2
- NM_000251.2(MSH2):c.2038C>T (p.Arg680Ter)
- NM_000251.2(MSH2):c.1906G>C (p.Ala636Pro)
MSH6
- NM_000179.2(MSH6):c.1634_1637del (p.Lys545fs)
- NM_000179.2(MSH6):c.892C>T (p.Arg298Ter)
- NM_000179.2(MSH6):c.1637_1638delAG (p.Glu546Glyfs)
- NM_000179.2(MSH6):c.2057G>A (p.Gly686Asp)
PMS2
- NM_000535.6(PMS2):c.903G>A (p.Lys301=)
- NM_000535.6(PMS2):c.903G>T (p.Lys301Asn)
- NM_000535.5(PMS2):c.861_864delACAG (p.Arg287Serfs)
- NM_000535.6(PMS2):c.1840A>T (p.Lys614Ter)
- NM_000535.6(PMS2):c.856delG (p.Asp286fs)

Carrier Status

Cystic Fibrosis (CF) carriers do not have CF but their children might. CF is an inherited condition that leads to a buildup of thick, sticky mucus that damages the lungs, pancreas, and other organs. This causes difficulty breathing and other potentially serious problems. If both biological parents are carriers of CF, then each of their children has a 1 in 4 chance of developing CF. Knowing whether they are a carrier of CF is especially important for people who are planning on having children.

Variants detected by microarray technology
CFTR
- NM_000492.3(CFTR):c.1521_1523delCTT (p.Phe508delPhe)
- NM_000492.3(CFTR):c.1519_1521delATC (p.Ile507del)
- NM_000492.3(CFTR):c.1000C>T (p.Arg334Trp)
- NM_000492.3(CFTR):c.1657C>T (p.Arg553Ter)
- NM_000492.3(CFTR):c.3484C>T (p.Arg1162Ter)
- NM_000492.3(CFTR):c.3718-2477C>T
- NM_000492.3(CFTR):c.2988+1G>A
- NM_000492.3(CFTR):c.1652G>A (p.Gly551Asp)
- NM_000492.3(CFTR):c.254G>A (p.Gly85Glu)
- NM_000492.3(CFTR):c.1585-1G>A
- NM_000492.3(CFTR):c.3846G>A (p.Trp1282Ter)
- NM_000492.3(CFTR):c.579+1G>T
- NM_000492.3(CFTR):c.1040G>C (p.Arg347Pro)
- NM_000492.3(CFTR):c.489+1G>T
- NM_000492.3(CFTR):c.3528delC (p.Lys1177Serfs)
- NM_000492.3(CFTR):c.1679G>C (p.Arg560Thr)
- NM_000492.3(CFTR):c.2657+5G>A
Sickle cell anemia carriers do not have sickle cell anemia but their children might. Sickle cell anemia is an inherited disease that affects red blood cells, which carry oxygen throughout the body. The disease causes red blood cells to change shape and no longer work well. That can lead to severe pain, vision problems, organ damage, stroke, and a shorter lifespan. If both biological parents are carriers of sickle cell anemia, then each of their children has a 1 in 4 chance of developing the condition. Knowing whether they are a carrier of sickle cell anemia is especially important for people who are planning on having children.

Variants detected by microarray technology
HBB
- NM_000518.5(HBB):c.20A>T (p.Glu7Val)
Tay-Sachs carriers do not have Tay-Sachs disease but their children might. Tay-Sachs disease is an inherited condition that leads to the deterioration of cells in the brain and spinal cord, typically leading to muscle weakness and death in early childhood. If both biological parents are carriers of Tay-Sachs disease, then each of their children has a 1 in 4 chance of developing the disease. Knowing whether they are a carrier of Tay-Sachs disease is especially important for people who are planning on having children.

Variants detected by microarray technology
HEXA
- NM_000520.5(HEXA):c.1421+1G>C
- NM_000520.5(HEXA):c.1274_1277dup (p.Tyr427Ilefs)
- NM_000520.5(HEXA):c.1073+1G>A
- NM_000520.5(HEXA):c.1073+1G>T

Heart and Blood Health

People with familial hypercholesterolemia have a higher chance than typical of developing very high levels of LDL cholesterol, which can increase the chance of a heart attack.

Variants detected by microarray technology
APOB
- NM_000384.2(APOB):c.10580G>A (p.Arg3527Gln)
- NM_000384.2(APOB):c.10580G>T (p.Arg3527Leu)
LDLR
- NM_000527.4(LDLR):c.551G>A (p.Cys184Tyr)
- NM_000527.4(LDLR):c.1444G>A (p.Asp482Asn)
- NM_000527.4(LDLR):c.1444G>T (p.Asp482Tyr)
- NM_000527.4(LDLR):c.2140+1G>A
- NM_000527.4(LDLR):c.2140+1G>T
- NM_000527.4(LDLR):c.1358+2T>A
- NM_000527.4(LDLR):c.2054C>T (p.Pro685Leu)
Hereditary hemochromatosis can lead to having too much iron in the blood. People with hereditary hemochromatosis can sometimes develop iron overload disorder, which happens when too much iron builds up in the body. Left untreated, elevated iron levels can lead to permanent organ damage.

Variants detected by microarray technology
HFE
- NM_000410.3(HFE):c.187C>G (p.His63Asp)
- NM_000410.3(HFE):c.845G>A (p.Cys282Tyr)
Hereditary thrombophilia can increase the chances of developing potentially dangerous blood clots. People with hereditary thrombophilia have a higher chance of developing blood clots inside veins when they shouldn’t. This can lead to health problems and, in some cases, be life–threatening.

Variants detected by microarray technology
F2
- NM_000506.4(F2):c.*97G>A
F5
- NM_000130.4(F5):c.1601G>A (p.Arg534Gln)

The role of genetics in determining risk.

Genetics is just one of many factors linked to developing a condition. If a variant is found for a particular condition, it means there is a higher chance of developing the health issues tied to that condition. Similarly, if no variants are found, the chance of developing a health issue can’t be ruled out. Healthcare providers should be consulted before any actions are taken based on AncestryHealth® reports.

There are resources to help.

We provide access to certified genetic counselors as part of our partnership with PWNHealth, and offer interactive webinars, direct messaging, or one-on-one counseling, where appropriate. These healthcare professionals can explain any notable findings and guide next steps, like earlier screenings. Reports are formatted to be printable and easy to share with a healthcare provider.

Have other questions? See our AncestryHealth Support Center.

AncestryHealth® includes laboratory tests developed and performed by an independent CLIA-certified laboratory partner, and with oversight from an independent clinician network of board-certified physicians and genetic counselors. The test results are not diagnostic and do not determine your overall chance of developing a disease or health condition. The tests are not cleared or approved by the U.S. Food and Drug Administration. You should consult a healthcare provider before taking any action based on AncestryHealth® reports, including before making any treatment, dietary, or lifestyle changes. AncestryHealth® is not currently available in New York, New Jersey or Rhode Island.