Secondary findings

While creating a new case, you can choose whether to include secondary findings for the proband. This option is available on the Family Tree screen → Create family tree panel → Show Secondary Findings.

Secondary findings are genetic variants that are not related to the primary indication for testing. These variants are automatically assigned the Incidental tag when they meet American College of Medical Genetics and Genomics (ACMG)-defined criteria for reportable secondary findings.

In Emedgene, the terms incidental findings and secondary findings both refer to ACMG-defined secondary findings. The platform continues to use the “incidental” label in certain places for technical consistency, though the modern standard is “secondary findings.”

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 except LOW
6. Affected gene: Listed in the ACMG SF v3.2 or 3.3 gene list for reporting secondary findings (PMID: 37347242, 40568962)

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.

ACMG SF v3.3 (2025 release; requires pipeline v100.39.0+)

Includes all v3.2 genes plus newly added genes:

• PLN
• ABCD1
• CYP27A1

This brings the total to 84 reportable genes.

Historical note

When Emedgene was first released, the term “incidental findings” was adopted in alignment with 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 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.

Warnings:

• Secondary findings are limited to the ACMG-defined gene lists. Variants outside these lists will not be tagged automatically.
• Only variants with adequate sequencing depth and quality are tagged. Low-quality calls may require manual review.