Template for Exome Report

1.  Abstract. The abstract should include the list of all the genes that are discussed in the variation section

2.  Clinical description. Provide full case report.

·  Mention sex, ethnicity, parental age, biometry at birth (and gestational age), biometry at last investigation - both with centiles and/or standard deviations, psychomotor development (if possible include IQ or DQ, with the test used and at what age), phenotype at last examination, current age, and all pertinent elements of clinical history.

·  Use the Standard Terminology proposed in Elements of Morphology or Human Phenotype Ontology (vide supra). Give pertinent family information.

3.  Methods: please include

·  Capture method

·  Type of sequencer

·  Variant analysis strategies (home-made pipeline, public tools…)

·  List of databases checked (Exome Variant Server, 1000 Genomes,…) and date on which the check was done.

4.  NGS quality report summary for each sample

Template of the quality report table (download xls file) to be inserted in the manuscript.

Proband / Add other family members (parents, sibs…) as appropriate
Total captured regions size / Mb
% of captured regions with coverage >10 / %
Average coverage of captured region (%) / %
Total number of SNPs
Total number of INDELs

5.  Variations of interest

5.1. Variations reported online

All variants that fulfill one of the technical and biological criteria below must be declared in DECIPHER prior to final acceptance. The ID number of the DECIPHER data must be declared here. Declaration to other databases may be added here as well.

A. Technical requirements

1.  For single nucleotide variations: coverage ≥10 in proband and relatives, with raw alignment checked in parents

2.  For indels: >5 variant reads and a variant/reference read ratio >0.3

B. Genetic conditions

1.  heterozygous variants/indel present in the proband and absent in unaffected parents and controls;

2.  homozygous variants/indel and hemizygous X variants never reported in public databases

3.  genes with two rare non synonymous variants/indel with mean allelic frequency <0.03, present in the proband, but not seen together in the parents and controls

The declaration is made using this DECIPHER xls file provided. All items, including those that are not mandatory for DECIPHER, must be completed, according to DECIPHER keywords. The main phenotypic traits must be added using HPO.

5.2. Subset of variations reported in the manuscript

Among variants, all variants that

·  have predicted pathogenicity (definite or probable) by at least one prediction program and

·  occur in genes that could be hypothesized to be associated with the phenotype based on current knowledge of gene function, pathway, expression pattern and suspected inheritance mode must be presented in a tabular form (see an example below with three type of variations) and discussed. All these variants must have been checked by Sanger sequencing in the proband and the relevant relatives, and must be further discussed in the text of this section.

Secondary/incidental findings in genes unrelated to the phenotype will not been reported.

Template for variants of interest (download xls file) to be inserted in the manuscript

Chromosome / chr1 / chr7 / chr12 / Etc…
Position / 239040006 / 45214519 / 45214604
Gene name / CDC27 / CES5A / MST1P9
refseq / NM_198317 / NM_005101 / NM_198576
Reference sequence / A / CAG / T
PROBAND: number of reads with reference / 12 / 58 / 0
PROBAND: alternative / T / --- / A
PROBAND: number of reads with alternative / 14 / 1 / 72
Other relative tested (NGS or Sanger) with the result / Father: absent (exome)
Mother: absent (exome)
Sib II-2: absent (Sanger) / Father: present (exome *+ Sanger)
Mother: absent (exome + Sanger)
Sib II-2: absent (Sanger) / Father: absent (exome + Sanger)
Mother: absent (exome + Sanger)
Sib II-2: absent (Sanger)
Mutation type / non sense / 5-UTR / intronic
Mutation: DNA (HGVS nomenclature _c.) / c.549A>T / c.1154+48delCAG / c.329+9T>A
Mutation: protein (HGVS nomenclature _p.) / p.Ala182* / Not relevant / unknown
Prediction SIFT / Damaging / Not predicted / Tolerated
Prediction < PolyPhen-2 / Deleterious / - / -
Prediction < * (add row per tool)

6.  Discussion. Present arguments as to why and how the candidate genes were selected.

7.  Facultative sections: Acknowledgements, online databases…

8.  References. Maximum 3 references per candidate gene.