PRC: Additional VCF related concepts commonly used to filter variants

[justinjj24]

Product Review Committee (PRC) reviewer Abeer Fadda (EGA bioinformatics QC lead) suggestion: include additional VCF related concepts commonly used to filter variants..

- Quality by depth (DP)
- Variant quality score (QUAL)
- Genotype qaullity (GQ)
- Fisher strand bias (FS)
- Allele balance (AB)
- Read Position Bias (ReadPosRankSum)

[justinjj24]

We agree with the suggestion. We initially focused for post variant calling level QC metrics on measurements that yield a single number (counts, ratios).

As these proposed additional metrics yields distribution, appreciating which associated statistic(s) (mean, median, variance, quantile distribution, …) will be most informative will need to be discussed amongst the WGS QC working group (akin some of our already included post alignment metrics such as “mean autosome coverage”, “average insert size”) to build consensus on how best to incorporate them, something we are very keen to include into our product development roadmap.

[justinjj24]

Workgroup consensus (Sep 2025 meeting):

The Product Review Committee (PRC) suggested incorporating additional VCF-level quality metrics (DP, QUAL, GQ, FS, AB, ReadPosRankSum) into the WGS-QC standards.

The workgroup acknowledged that while these are widely used and well-defined in the VCF specification, they are inherently site- or variant-specific and do not scale meaningfully to global genome-level QC. Attempting to aggregate or set universal thresholds would risk oversimplification, variability across sequencing technologies, and potential misinterpretation.

The group emphasized that WGS-QC standards should remain focused on sequencing-level quality metrics that reliably determine whether a genome is of sufficient quality for downstream use. Variant-level QC remains more appropriate for local or pipeline-specific applications rather than for a global QC benchmark.

Decision:

The workgroup agreed to gently push back on the PRC recommendation. These VCF-related metrics will not be included in Roadmap V2 of WGS-QC standards, as they provide limited value at the global standardization level. Instead, focus will remain on sequencing-based QC metrics with broad applicability and high interpretability. The option to revisit variant-level metrics in future iterations remains open if practical methodologies emerge.