Clinical features prompting consideration of clinical testing for a germline predisposition allele(s)
| Clinical features . |
|---|
| Personal history of ≥2 cancers, 1 of which is a hematopoietic malignancy (order does not matter) |
| Personal history of a hematopoietic malignancy plus: • Another relative within two generations with another hematopoietic malignancy, or • Another relative within two generations with a solid tumor diagnosed at age 50 or younger, or • Another relative within two generations with other hematopoietic abnormalities |
| Presence of a deleterious gene variant in tumor profiling that could be a germline allele, especially if that variant is present during remission* |
| Age of diagnosis of hematopoietic malignancy at an earlier age than average (eg, MDS diagnosed ≤ 40 y) |
| Germline status of a variant is confirmed by: |
| Its presence in DNA derived from a tissue source not likely to undergo somatic mutation frequently (eg, cultured skin fibroblasts or hair follicles) AND at a variant allele frequency consistent with the germline (generally considered between 30-60%), or |
| Its presence in at least two relatives at a variant allele frequency consistent with the germline |
| Clinical features . |
|---|
| Personal history of ≥2 cancers, 1 of which is a hematopoietic malignancy (order does not matter) |
| Personal history of a hematopoietic malignancy plus: • Another relative within two generations with another hematopoietic malignancy, or • Another relative within two generations with a solid tumor diagnosed at age 50 or younger, or • Another relative within two generations with other hematopoietic abnormalities |
| Presence of a deleterious gene variant in tumor profiling that could be a germline allele, especially if that variant is present during remission* |
| Age of diagnosis of hematopoietic malignancy at an earlier age than average (eg, MDS diagnosed ≤ 40 y) |
| Germline status of a variant is confirmed by: |
| Its presence in DNA derived from a tissue source not likely to undergo somatic mutation frequently (eg, cultured skin fibroblasts or hair follicles) AND at a variant allele frequency consistent with the germline (generally considered between 30-60%), or |
| Its presence in at least two relatives at a variant allele frequency consistent with the germline |
Certain gene alleles (eg, CHEK2 I200T and truncating DDX41 variants) are overwhelmingly likely to be germline and should prompt consideration of germline testing when identified even once.