Glossary

ACMG : the American College of Medical Genetics and Genomics

AMP : the Association for Molecular Pathology

Breakpoint : indicates the genomic coordinate where a CNV begins or ends.

ClinVar : NCBI's public database about relationships among human variation and disease.[ Link ]

ClinVar assertions : used to annotate retrieved variant calls with their clinical significance, conditions and review status values.

ClinVar review status values
(NA) : No assertion provided
(NC) : No assertion criteria provided
(S) : Criteria provided single submitter
(M) : Criteria provided multiple submitters no conflict
(C) : Criteria provided conflicting interpretations
(E) : Reviewed by expert panel
(G) : Practice guideline

ClinVar significance
Following recommendations of the ACMG and AMPhttps://www.ncbi.nlm.nih.gov/pubmed/25741868, there are five standard terms for variants interpreted for Mendelian disorders: Benign, Likely benign, Uncertain significance, Likely pathogenic, and Pathogenic. Other terms are: drug response, association, risk factor, protective, affects, conflicting data from submitters, other , and not provided. For explanations of all terms in detail, please visithttps://www.ncbi.nlm.nih.gov/clinvar/docs/clinsig/

CNVs : Copy Number Variations; gain or loss of segments of genomic DNA relative to a reference; also called 'Structural Variation.'

Impact : putative variant impact on the protein-coding potential of a gene, as predicted by SnpEff.

Impact categories : must be used with care; they were created only to help and simplify the filtering process. There is no way to predict whether a HIGH impact or a LOW impact variant is the one producing a phenotype of interest.

Impact

Meaning

Example

HIGH

The variant is assumed to have high (disruptive) impact in the protein, probably causing protein truncation, loss of function or t riggering nonsense mediated decay.

stop_gained, frameshift_variant

MODERATE

A non-disruptive variant that might change protein effectiveness.

missense_variant, inframe_deletion

LOW        

Assumed to be mostly harmless or unlikely to change protein behavior.

synonymous_variant

MODIFIER

Usually non-coding variants or variants affecting non-coding genes, where predictions are difficult or there is no evidence of impact.

exon_variant, downstream_gene_variant

SNP : Single-Nucleotide Polymorphism

SnpEff : A program for annotating and predicting the protein-coding effects of single nucleotide polymorphisms [ Link]

SNVs : Small Nucleotide Variants (include SNPs, small insertions and deletions)

Structural Variation – see CNVs

Variants : In a typical sequencing experiment, you will find many places in the genome where your sample differs from the reference genome. These are calledgenomic variants or just variants.