Exome sequencing errors resulting in misdiagnosis?

Question

[Sarah]

Hello,

Can exome sequencing lead to misdiagnosis (false-positive result) of unidentified Mendelian disease if variant is found in a gene which can also have deleterious variants in control or healthy people?

What can explain the presence of high frequency of healthy people with deleterious mutations in Mendelian disease gene in exome variants server (EVS)? Given that Mendilan diseases are so rare (low prevalence) to be seen at high frequency in quite small cohort

Answer 1

[Zev.Kronenberg]

1. Pipeline bias.
2. Shared false variant calls.
3. The variant is not damaging.
4. Errors in estimating the allele frequency (different sample sizes at a position)
5. Wrong annotation.
6. Many more....

[JC]

7. Contribution of multiple SNPs in complex diseases.

[Matt Shirley]

8. Somatic mutation is damaging only in a specific tissue type.

[Katie D'Aco]

9. Low penetrance disease SNP's