If we have a clear profile of mutation, we will have to apply these filters on BiERapp to get directly the possible causal mutation. Sometimes we have several interesting profiles of mutations, not only one. For this case we should explore these different scenarios and decide the best prioritization strategy.

To know better this web tool, we propose you two groups of activities:

• In the part A of this activity, we would have to apply individual filters. This action give us information about the effect of each filter (maybe there are some filters more powerful than other). After each filtering, we have to clear the filter to apply the next one.
• In the part B of this exercise, we have a real selection where we combine several filters at the same time. It is interesting to know how the number of variants is reducing, when applying a progressive group of filters (without deleting the previous filter). We want to know the accumulative effect of several filters (all together).

1. Total number of variants without filters
2. Recessive heritage
3. Dominant heritage (mother is affected)
4. What chromosome includes more variants 4,6 or 8?
5. For these genes: RET and BRCA2
6. Any variant for this SNPId: rs1800858? Explore detailed information in the direct link to Ensembl website. Are there other synonyms variants?
7. Description of variants. How many MNVs?
8. Variants with MAF (Minimum Allelic Frequency) < 0.001 for European American population in ESP 6500
9. Variants with MAF (Minimum Allelic Frequency) < 0.001 for African American population in ESP 6500
10. Variants with the two preview MAFs at the same time

1. Several filters to apply:
   • “De novo” mutations
   • SIFT < 0.05
   • Download these final results in a csv file.
2. Other prioritization strategy:
   • Variants in this BED file: neuro_diseases.bed (you have to download this file and upload in BiERapp).
   • Polyphen > 0.95

Some of these solutions could be different when having updated databases

1. Candidate variants: 40000
2. Candidate variants: 1588
3. Candidate variants: 6022
4. Candidate variants: chr4 1743; chr6 2685; chr8 1338
5. Candidate variants: 19
6. Candidate variants: 1; 11 synonyms variants in this link
7. 13 MNVs
8. Candidate variants in European American population, ESP 6500: 19726
9. Candidate variants in African American population, ESP 6500: 19680
10. Candidate variants in the two previous MAFs: 19482

1. Candidate variations: 118→3
2. Candidate variations: 17→2