Duplication Mutation prediction

Question

[Yoosef]

Hello everyone... I need to predict a duplication mutation error with mutation taster. what i understand from mutation taster help , it can't predict duplication mutations like c.1312dupC . Is there a way to use that for duplication mutations? If not, please introduce me proper database. also please help how can i insert intronic mutation like c.1682-1G>C in that database. Thanks a lot.

Answer 1

[Kevin Blighe]

Almost all in silico pathogenicity / functional impact prediction algorithms that have been developed have been developed for single nucleotide variants, whether coding or non-coding. However, algorithms that claim to be able to predict the impact of indels (your duplication event can be regarded as an insertion of C) have been appearing relatively recently, including:

• A comprehensive study of small non-frameshift insertions/deletions in proteins and prediction of their phenotypic effects by a machine learning method (KD4i)
• Assessing the Pathogenicity of Insertion and Deletion Variants with the Variant Effect Scoring Tool (VEST-Indel)
• DDIG-in: discriminating between disease-associated and neutral non-frameshifting micro-indels
• SIFT Indel: Predictions for the Functional Effects of Amino Acid Insertions/Deletions in Proteins

I'm linking you to the published manuscript relating to each tool, here. There are web-based implementations of these too.

In order to use these, you will most likely have to convert your HGVS format to something like, for example, chr start end ref alt. This program, implemented in Python, can apparently do just that: https://github.com/biocommons/hgvs

Kevin

[Yoosef]

I am so grateful for your help Mr glighe.