Incidental (secondary) findings

Add new case page > Family tree screen > Create family tree panel > Show Secondary Findings

While creating a case, you can choose if you want Secondary findings in the Proband to appear in the results.

Secondary findings are variants that are automatically assigned the Incidental tag when they meet the criteria for secondary findings as defined by the American College of Medical Genetics and Genomics (ACMG).

Tagging criteria

A variant is automatically tagged as a secondary finding if it meets all of the following criteria:

1. Classification: Previously classified as pathogenic or likely pathogenic in ClinVar or Curate variant databases

2. Zygosity: Heterozygous or homozygous (only homozygous for the HFE gene)

3. Allele frequency: Less than 5%

4. Read depth: 10× or higher

5. Variant quality: Any value but LOW

6. Affected gene: Listed in the ACMG SF v3.2 medically actionable gene list for reporting secondary findings in clinical exome and genome sequencing (PMID: 37347242)

ACMG SF v3.2 gene list

ACTA2, ACTC1, ACVRL1, APC, APOB, ATP7B, BAG3, BMPR1A, BRCA1, BRCA2, BTD, CACNA1S, CALM1, CALM2, CALM3, CASQ2, COL3A1, DES, DSC2, DSG2, DSP, ENG, FBN1, FLNC, GAA, GLA, HFE, HNF1A, KCNH2, KCNQ1, LDLR, LMNA, MAX, MEN1, MLH1, MSH2, MSH6, MUTYH, MYBPC3, MYH11, MYH7, MYL2, MYL3, NF2, OTC, PALB2, PCSK9, PKP2, PMS2, PRKAG2, PTEN, RB1, RBM20, RET, RPE65, RYR1, RYR2, SCN5A, SDHAF2, SDHB, SDHC, SDHD, SMAD3, SMAD4, STK11, TGFBR1, TGFBR2, TMEM127, TMEM43, TNNC1, TNNI3, TNNT2, TP53, TPM1, TRDN, TSC1, TSC2, TTN, TTR, VHL, WT1.

In Emedgene, the terms "incidental findings" and "secondary findings" both refer to secondary findings as defined by the ACMG, due to historical usage.

When Emedgene was first released, the term “incidental findings” was adopted in alignment with the clinical genomics standard at the time. The 2013 ACMG recommendations defined incidental findings as “the results of a deliberate search for pathogenic or likely pathogenic alterations in genes that are not apparently relevant to a diagnostic indication for which the sequencing test was ordered” (PMID: 23788249).

As the field evolved, the ACMG and broader clinical community began to distinguish between “incidental findings” (unexpected, not actively sought) and “secondary findings” (intentionally analyzed and reportable). This shift was reflected in the updated 2016 ACMG guidance (PMID: 27854360).

To reflect this change, Emedgene introduced the term “secondary findings” into the platform. However, “incidental findings” remains in use throughout the platform for technical consistency.