CARRIER SCREENING

Discover the evidence behind our flagship product

Counsyl is committed to sharing our pioneering work on carrier screening with the scientific community. Explore the peer-reviewed evidence showing the value of carrier screening.

Foresight Value

Foresight Value

How does Foresight maximize detection of couples at-risk of passing down serious diseases?

Society Guidelines

Do professional societies recognize the utility of expanded carrier screening and provide guidance?

Analytic Validity

Can Foresight accurately detect whether a specific genetic variant is present or absent?

Clinical Validity

Can Foresight accurately identify couples at-risk of passing on serious genetic conditions?

Clinical Utility

Does Foresight provide actionable information that can improve health outcomes?

Counsyl Foresight™ Carrier Screen Value

Foresight maximizes detection of couples at-risk of passing down serious diseases through purposeful panel design and superior technology.

At-risk Couple Detection

Observational data shows that 1 in 22 couples in the US will be at-risk of passing down a serious, childhood disease on the Foresight expanded panel.1

Clinician-Designed Panels

Counsyl offers an expanded panel with 176 diseases that meet specific inclusion criteria,2 as well as smaller sub-panels such as cystic fibrosis and spinal muscular atrophy.

Superior Technology

Comprehensive detection rates for the vast majority of genes on our panel (>99% across ethnicities)1 means you can trust both positive and negative results.

Current medical policies miss a significant percentage of pregnancies affected with serious inherited conditions that are detected by expanded carrier screening

For example, the largest (>340,000 patients) published study on expanded screening shows the percentage of affected pregnancies, per ethnicity, missed by ethnicity-based policies:

East Asian

94%

Hispanic

79%

Northern European

65%

Ashkenazi Jewish

55%

Prioritizing clinical significance in panel design2

Our experts evaluated >650 genes based on strict criteria in an effort to produce not simply more, but meaningful clinical information.

 

Superior technology

The custom technology employed by Foresight leads to exceptional detection rates for all included diseases.

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Foresight’s CF carrier detection rates compared with those of 23 mutation screen1,4

For example, Foresight detection rates for cystic fibrosis (CF) exceed those of the limited mutation panels that are covered by most medical policies.3 Limited mutation panels particularly overlook the CF disease risk for non-European individuals.3,4

Society Guidelines

The American College of Obstetricians and Gynecologists (ACOG) has issued committee opinions on carrier screening that align with Counsyl’s approach5,6

Expanded carrier screening is an acceptable strategy for carrier screening5
At a minimum, cystic fibrosis and spinal muscular atrophy, should be offered universally6

In alignment with ACOG, all conditions screened for by Foresight meet several of the following consensus-determined criteria:6

Analytic Validity

Can the test accurately detect whether a specific genetic variant is present or absent?

In a peer-reviewed validation study on expanded carrier screening, we demonstrate that using our unique methodology, Foresight identifies different types of genetic mutations ranging from single base pair substitutions to large copy number variants with high accuracy. Validation showed an analytical sensitivity of >99% and analytical specificity of >99%.11

Observed Foresight test performance metrics:1

CARRIERS AT-RISK COUPLES
Panel-wide FP rate 1 in 4,166 1 in 506,637
Average disease-level FP rate 1 in 1,136,000 1 in 293,505,998
Panel-wide PPV 99.963% 99.988%
Average disease-level PPV 99.939% 99.878%
Panel-wide NPV 99.930% >99.999%

Foresight achieves a high positive predictive value (PPV) on rare genetic diseases. Panel-wide, the chance of a false positive (FP) is 0.024%.1

Clinical Validity

Can the test accurately identify couples at-risk of passing on serious genetic conditions?

Clinical experience has been initially assessed by screening 36,845 patients and shows that 1 in 300 pregnancies in the US will be at-risk for a child with a serious genetic disease on the Foresight panel.1,7-9

Variant Curation

A Critical Measure of Clinical Validity
The variant curation team is made up of 30 expert variant curators with over 120 years of combined curation experience. To ensure clinical validity, we have developed a robust variant classification protocol that takes into account multiple lines of evidence including published literature and public databases.

Variants of Uncertain Significance
We use the ACMG and AMP joint guidelines10 which provide specific guidance on variant interpretation. We only report the presence of variants that have sufficient evidence to be classified as pathogenic or likely pathogenic. Variants of uncertain significance are not reported on Foresight.11

Clinical Utility

Does the test provide actionable information that will improve outcomes?

ACOG has recognized that prenatal genetic testing has established clinical utility;11

Reassures patients when results are normal,
Identifies disorders for which prenatal treatment may provide benefit,
Optimizes neonatal outcomes by ensuring the appropriate location and personnel for delivery, and
Allows for informed decision making during pregnancy

Carrier screening allows expectant couples to pursue prenatal diagnosis and preconception couples to take steps prior to pregnancy to ensure the birth of an unaffected child.11

76% of couples at-risk for severe or profound conditions used their results to make decisions about their reproductive plans1,2

Learn how couples use their expanded carrier screening results in The Journal of Genetic Counseling

CONNECT WITH US

Interested in speaking to a policy specialist about updating your medical policy?

FAQ

How many diseases are included on the Counsyl ForesightTM Carrier Screen?

The Foresight Carrier Screen includes screening for 176 autosomal recessive and X-linked diseases. A full list of conditions can be found at counsyl.com/diseases.

What is the at-risk couple detection rate of Foresight and why does this matter?

The true goal of carrier screening is to identify couples at high-risk of passing down a serious, childhood onset condition to their children. Therefore, the true value of an expanded carrier screening panel is not how many diseases it includes, but how likely it is to identify an at-risk couple of a serious disease. As a result of disease-selection and our unique methodology, 1 in 22 couples screened at Counsyl will be identified as high-risk, based on observational data.

Can a provider order fewer than 176 genes?

Yes, providers can customize a panel from the 176 genes that are available. Some providers prefer to order a smaller subset of conditions, such as cystic fibrosis and spinal muscular atrophy.  Single gene testing is commonly used for partner screening.

Who is the intended population?

In accordance with ACOG guidelines,5 Foresight is appropriate for any individual who is pregnant or planning a pregnancy and has not previously been screened.

Why is it important to routinely screen for rare diseases?

Collectively, the diseases on the Foresight Carrier Screen have an incidence of 1 in 300 in the general population, which is more common than conditions like Down syndrome (1 in 800) and open neural tube defects (1 in 1,000) for which prenatal screening is routine.1 Of children born with genetic diseases, 80% have no significant family history due to the nature of recessive inheritance.13 Finally, genetic diseases pose a significant burden of morbidity, mortality, and cost. In the US, 18% of childhood hospitalizations are due to genetic diseases.14

Is expanded carrier screening recommended by medical societies?

Yes. The American College of Obstetricians and Gynecologists (ACOG) recognizes the utility of prenatal and preconception genetic screening11 and states that ethnicity-based screening, panethnic screening, and expanded carrier screening are all acceptable strategies5. ACOG also provides guidance for the types of diseases to be included on expanded panels and Foresight complies with these guidelines.5

Has the Foresight Carrier Screen been analytically validated?

Yes, our peer-reviewed validation study demonstrated that Foresight identifies mutations ranging from single base pair substitutions to large copy number variants with > 99.99% analytical sensitivity, > 99.99% specificity, > 99.99% accuracy, and > 99.99% reproducibility. Foresight also achieves a high positive predictive value on rare genetic diseases.  The chance of a false positive on the Foresight screen is 0.024%.1

What criteria does Counsyl use to select diseases for the Foresight Carrier Screen?

Diseases were systematically selected based on actionability, severity, prevalence, and clinical sensitivity, meaning a high detection rate (>90%) is achievable given available technology.2 Foresight does not screen for diseases that typically have a mild presentation or adult-onset. While we do not have a cut-off for disease incidence, extremely rare diseases, for which only a handful of case reports exist, are excluded. All the genes on Foresight have an established clinical validity (gene-disease association).

Does Foresight improve health outcomes or impact reproductive management?

Based on a retrospective survey, 76% of couples at-risk for having a child with a serious genetic disease altered their reproductive plans, for example, by pursuing prenatal diagnosis or using in-vitro fertilization with preimplantation genetic testing.12

Will using a full exon sequencing methodology detect variants of uncertain significance (VUS) and how does Counsyl handle the reporting of VUS information?

While the methodology utilized by the Foresight Carrier Screen can detect variants of uncertain significance, Counsyl only reports disease-causing or likely disease-causing variants, in accordance with the American College of Genetics and Genomics (ACMG) guidelines.10 Reporting of VUS results as a part of routine screening is not standard among laboratories performing expanded carrier screening.11

References

  1. Hogan G, et al. 2018. Validation of an Expanded Carrier Screen That Optimizes Sensitivity via Full-Exon Sequencing and Panel-Wide Copy Number Variant Identification. Clin Chem https://doi.org/10.1373/clinchem.2018.286823.
  2. Beauchamp K, et al. 2017. Systematic design and comparison of expanded carrier screening panels. Genet Med doi:10.1038/gim.2017.69.
  3. Beauchamp K, et al. 2016. Comparing the clinical yield of carrier screening: genotyping versus exon sequencing. Poster presented at: NSGC Annual Education Conference; Seattle, WA
  4. Amos J, et al. 2006. Technical Standards and Guidelines for CFTR Mutation Testing. Genet Med 1–28.
  5. "Carrier screening in the age of genomic medicine. Committee Opinion No. 690. American College of Obstetricians and Gynecologists.” Obstet Gynecol 2017;129:e35–40
  6. “Carrier screening for genetic conditions. Committee Opinion No. 691, March 2017. American College of Obstetricians and Gynecologists.” Obstet Gynecol 2017;129:e41–55
  7. de Graaf G, et al. 2015. Estimates of the Live Births, Natural Losses, and Elective Terminations with Down Syndrome in the United States. Am J of Med Genet. Part A 167A (4): 756–67.
  8. Parker S, et al. 2010. Updated National Birth Prevalence Estimates for Selected Birth Defects in the United States, 2004--2006. Birth Defects Research. Part A, Clinical and Molecular Teratology 88 (12): 1008–16.
  9. American Thoracic Society website.https://www.thoracic.org/patients/patient-resources/breathing-in-america/resources/chapter-7-cystic-fibrosis.pdf. Accessed July 30, 2018.
  10. Richards S, et al. 2015. Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17 (5): 405–24.
  11. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics, Committee on Genetics, and Society for Maternal–Fetal Medicine. 2016. “Practice Bulletin No. 162: Prenatal Diagnostic Testing for Genetic Disorders.” Obstet Gynecol 127 (5): e108–22.
  12. Ghiossi C, et al. 2017. Clinical Utility of Expanded Carrier Screening: Reproductive Behaviors of At-Risk Couples. J Genet Couns, September. https://doi.org/10.1007/s10897-017-0160-1.
  13. Blythe S, et al. 1984. Advances in the Diagnosis and Management of Cystic Fibrosis. Clin Biochem 17 (5): 277–83.
  14. Kingsmore S. 2012. Comprehensive carrier screening and molecular diagnostic testing for recessive childhood diseases. PLoS Curr 4:e4f9877ab8ffa9.