CNV classification

[davmlaw]

Talked to Lucas and Kerryn about CNV classifications

They use 2020 ACMG CNV guidelines

Biggest questions are:

• Is gene LOF
• If CNV is not whole gene, then is it in frame or not?

They generally look in gnomadSV to see if common, and ClinVar

Can classify single exon. NGS is for smaller resolution. Often have cyto look at them first

Del much more common for disease causing. As dup needs GOF

Usually looking for overlapping OMIM gene. Rare to report on multiple genes for an event (but possible)

Coordinates

• Don't usually provide HGVS or coordinates - usually just report on gene or exons eg (deletion of exons 1-7)
• Don't usually report copy number just del/dup (in LOF/GOF gene)
• They don't usually use ISCN

Useful information to retrieve

ClinVar CNV del/dup (separate) counts for gene gnomAD del/dup (separate) counts for gene

Extra Evidence keys

• Cyto confirmation
• MLPA confirmation
• Above useful annotation?

Overlaps

When looking in ClinVar, gnomad SV or thinking about Shariant overlaps, they are happy to be very course, eg gene or exon level overlaps.

[davmlaw]

Grace sent me some sample data - Thurs 2/11/2023