Origin¶
Presumed source of the variant in the context of this study.
Understanding Variant Origin¶
The origin of a variant in a study is important for interpreting the results in context. Studies may provide specific information about the origin of the variant (somatic with tumor/normal paired data) while others may be more ambiguous (tumor-only sequencing with a variant that may be somatic or germline, e.g., BRCA1 mutation from a breast cancer sample). Documenting Variant Origin allows for quick filtering of evidence and provides context for the study compared to other studies that involve that variant.
Curating Variant Origin¶
The Variant Origin in and Evidence Item identifies whether the variant was presumed as an inherited (germline mutation) or acquired (somatic mutation) event in the context of the study. We generally consider somatic events to be the priority, as this is an area that has not been as well addressed by existing resources. However, germline mutations with established clinical relevance are acceptable. Germline polymorphisms (>1% allele frequency in the population) are considered low priority, again unless there is an established clinical relevance. We encourage the use of large population resources such as gnomAD for population frequency estimations rather than relying on the frequency reported by the original study. Polymorphisms described in association studies should be curated with great caution and may face additional scrutiny from CIViC moderators. For some variant types, the variant origin field may be unknown or N/A. For example, EXPRESSION variants are neither germline nor somatic and should be marked as N/A. Fusion variants are an unusual case in that they are often observed in the transcriptome but are usually accompanied by an underlying somatic (or germline) mutation. Most fusions should be entered as somatic. If in doubt, please note the issue at the time of your submission to encourage discussion during the moderation stage.
Expression variants should be marked as ‘N/A’.
Fusions are often observed in the transcriptome but are usually accompanied by an underlying somatic (or germline) mutation.
Population frequencies should be based on current population databases (e.g., gnomAD) rather than the original report.
Origin |
Icon |
Description |
|---|---|---|
Somatic |
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Variant is a mutation, found only in tumor cells, having arisen in a specific tissue (non-germ cell), and is not expected to be inherited or passed to offspring. |
Rare Germline |
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Variant is found in every cell (not restricted to tumor/diseased cells) and is thought to exist in less than 1% of the population relevant to this evidence item. |
Common Germline |
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Variant is found in every cell (not restricted to tumor/diseased cells) and is thought to exist in at least 1% of the population relevant to this evidence item. |
Combined |
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Variants in the corresponding Complex Molecular Profile have heterogeneous origins. |
Unknown |
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The variant origin is uncertain based on the available evidence. |
N/A |
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The variant type (e.g., expression) is not compatible (or easily classified) with the CIViC concept of variant origin. |
Examples
Somatic |
DNAJB1-PRKACA (EID532), BRAF V600E (EID1409), KRAS Exon 2 Mutation (EID993), EGFR Amplification (EID473) |
Rare Germline |
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Common Germline |
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Unknown |
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N/A |