In 2020, a major laboratory upgraded the CDKN2A c.146T>C (p.I49T) variant to variant to “likely pathogenic” (LP). This prompted reevaluation of internal data and consultation with other major laboratories regarding their current classifications of the variant to determine how to appropriately provide cancer screening recommendations for individuals with this variant, as well as their families. It became clear there was still a discrepancy in classification and further evaluation was needed to clarify the significance of this CDKN2A variant. To help inform the cancer phenotype of this variant, a collaboration was formed between the Cancer Genetics groups from Stanford, UCLA, UCSF, USC, and UT Southwestern - centers that serve a significant number of patients who are Hispanic/Latino, especially those of Mexican ancestry. We will review the primary findings from this research collaboration as well highlight psychosocial issues, insurance considerations, importance of anticipatory guidance surrounding secondary findings, and the complexities of counseling about a variant with discrepant classifications and limited phenotype data by using case examples. We hope this brings awareness to the ongoing complexities and nuances of managing patients' care with the CDKN2A p.I49T variant, as well as the role of a genetic counselor in navigating uncertainty. 

Presented by: 

NSGC Cancer SIG Antiracism Subcommittee
Ashlie Browning, MS, CGC
Charité Ricker, MS, CGC
Daisy Hernandez, MS, CGC 

Date: June 11, 2025 

Learning Objectives: 

1. Review the status of discordant classifications of the CDKN2A I49T variant (2020-current).
2. Highlight the primary goal of a collaborative research effort and summarize our main findings.
3. Illustrate case examples and identify common counseling challenges associated with CDKN2A I49T.
4. Discuss the psychosocial challenges CDKN2A I49T may have on Hispanic/Latino (H/L) patient populations 

Continuing Education Unit Approval: 

The National Society of Genetic Counselors (NSGC) has authorized National Society of Genetic Counselors (NSGC) to offer up to 1 Category 1 contact hours for CDKN2A p.I49T – to screen or not to screen?. The American Board of Genetic Counseling (ABGC) will accept CEUs earned at this program for the purposes of genetic counselor certification and recertification. 

Successful Completion: 

1. View recording
2. Pass quiz
3. Complete evaluation