Content Comparison

...

• https://docs.google.com/spreadsheets/d/1M9a74RyVOjUAUCQIlUXFyFAaNANkdwPJEHT0FYxH9-4/edit#gid=487083693

• Segregation calculator

• Splice AI lookup

  • Demo version with new features

• https://liftover.broadinstitute.org/

• Other helpful resources:

  • ACMG / AMP Guidelines, Richards 2015

    • https://docs.google.com/presentation/d/15LyMNNcODtNMjU4pa1PkhywChSWX1Um3CVx4HjX0L-0/edit#slide=id.p

    • https://docs.google.com/presentation/d/1lUZcHfwopn-Bo7k67hgRWe-CREVEZTo0xMFN-wqb0vU/edit#slide=id.g2827f193e86_0_1

  • PVS1 paper - Tayoun et al. 2018 https://drive.google.com/open?id=18DLSzEt5iUDVNYqGZYpcZK6lrSP3Y6Uz&usp=drive_fs

  • Splice consensus sequence

  • TGG Variant Curation SOP

  • ACMG SF v3.2 (2023)

• CNVs

  • Nomenclature in Fabric (notes from 01.08.24).

    • INTERGENIC variants: Chr#:g.####-####del

      • Example: chr17:g.29517928-31373373del in case D-061109681-BH-4009-P-A

      • The header will read “A pathogenic structural variant involving several genes was identified.”

    • INTRAGENIC variants: NM_###(GENE):c.###_###del

      • Example: NM_018055.5( NODAL):c.193+ 290_194-799del in case E3710317398

      • The header will read “A likely pathogenic structural variant involving NODAL was identified.”

  • Editing parental origin, size, number of genes:

    • 

  • https://search.clinicalgenome.org/kb/gene-dosage?page=1&size=25&search=

  • https://cnvcalc.clinicalgenome.org/redmine/projects/cnvcalc/cnv_calculator/cnv-loss

  • https://docs.google.com/document/d/1m4oLaScW88S5p5YUxBAfNZqK8bNOBAQEDQfyXiZycKc/edit#heading=h.ftj7oc7qj5cy

Multinucleotide variants (FE2) - see last bullet in “Write Report” section of the workflow SOP

• Fabric is inflexible when it comes to reporting multinucleotide variants that are chopped up in the VCF. There are manual touches to fix the report as best to our ability:

  • Email support@fabric.com to request a fix to the variant table

  • The variant header on the report is hard coded and cannot be edited. ie - “This patient is heterozygous for variant p.XXX in the XXGENE gene.” as displayed in the drafting page, and “ARHGAP31 NM_020754.3: c.2095_2096del (p.Pro699TrpfsTer21) [chr3:119132870 (GRCh37)] on the PDF report.

  • In the variant evidence summary, you will need to write an explanation for the nomenclature discrepancy. Example:

  • Please note: the variant nomenclature has been corrected to ARHGAP31 c.2095_2101delinsTGTG, p.Pro699_Ser701delinsCysGly based on multiple variants in cis impacting the same codons

Gene Curation

• Curation template

• https://docs.google.com/spreadsheets/d/1X71XG1qz3YqJWFM6iaJY7tcAUaFyeF3UIj3mC7EVmUs/edit#gid=0 - please add your summaries that are reported out here

...