Summary section

The Summary section highlights core variant-related information from other Variant page sections:

• Clinical Significance section (Variant Info, In silico Prediction, Gene's related diseases, Clinical significance),

• Quality section (Quality),

• Population Statistics section (Population Summary),

• Evidence section (Variant Interpretation, ACMG Classification, Pathogenicity).

Each of the Summary section cards has a button linking to its original location on the Variant page where you can see more details and/or edit the evidence.

Let's look closer at each of the cards:

1) Variant Interpretation

Notes added automatically or manually in the Evidence section. Shown only if not empty.

2) Variant Info

• Sequence variant (SNV/Indel), mtDNA variant (SNV/Indel): main effect*,* gene symbol, if available - HGVS descriptions on coding DNA and protein levels.

* CNV (DEL/DUP): CNV length, variant type, number of genes involved, list of gene symbols. If the gene list is partial, you may hover over it to see the full list.

3) Quality

• Sequence variant (SNV/Indel), mtDNA variant (SNV/Indel), STR:

  • variant caller (32.0+),

  • sample name,

  • zygosity,

  • depth of coverage,

  • percentage of alternative allele reads,

  • overall variant quality.

• CNV (DEL/DUP):

  • variant caller (32.0+),

  • sample name,

  • zygosity,

  • overall variant quality.

4a) Population Summary

Population statistics from gnomAD (calculated for the combined gnomAD population including both exome and genome samples):

• Total AF - overall alternative allele frequency,

• Allele count - Counts of alternative allele (or Homoplasmy Count for mtDNA variants),

• Hom/Hemi count - Counts of alternative allele in homozygous or hemizygous state (or Heteroplasmy Count for mtDNA variants),

• Max AF - the highestalternative allele frequency among gnomAD populations;

Population statistics from organization databases (if available):

• Allele count - Counts of alternative allele,

• Hom/Hemi count - Counts of alternative allele in homozygous or hemizygous state.

4b) STR repeats distribution (2.28+)

STR repeats distribution displays allele counts in gnomAD and 1000 Genomes Project, as well as gnomAD pathogenicity ranges.

5) Gene's related diseases

• Number of gene-disease connections for this gene within Emedgene knowledge base,

• Disease name,

• Disease inheritance mode,

• Link to the gene-disease connection source(s),

• Number of patient's phenotypes matching disease phenotypes out of the total. Note: displayed by default for automatically tagged variants; for manually tagged variants you need to first trigger automatic generation of the evidence by entering the variant's Evidence page.

6) Pathogenicity

Here you can see manually-assigned variant Pathogenicity, change it or select one from the dropdown if it's empty.

7) Clinical significance

This card highlights previous pathogenicity classifications in public and your private variant databases including Curate. Each classification source is represented by one badge. Uncertain and Other classifications are only shown if there are no Benign/Likely Benign and/or Pathogenic/Likely Pathogenic classifications of this variant in a particular database.

8) ACMG Classification

Showcases ACMG tags assigned to the variant and the resulting classification.

• Sequence variant (SNV/Indel), mtDNA variant (SNV/Indel)

  • before 32.0: the final class and the criteria used.
  • 32.0+: the final class, the criteria used and the score.

• CNV (DEL/DUP)

9) In silico Prediction

Overall estimations of in silico prediction results.

• Small variant (SNV): Missense Prediction, Conservation, Splicing Prediction;

• Small variant (Indel): Conservation;

• mtDNA (SNV/Indel): Missense Prediction;

• CNV (DEL/DUP), SV, STR: not available.