Proposed system for "binning" of secondary findings from genome sequencing

	Criteria:	Clinical utility	Clinical validity			Unknown clinical implications
G e n e s	Bins:	Bin 1 Medically actionable information	Bin 2A Low risk information	Bin 2B Medium risk information	Bin 2C High risk information	Bin 3 All other loci
	Examples:	BRCA1/2 MLH1, MSH2 FBN1 NF1	PGx variants and common risk SNPs	APOE Carrier status for recessive Mendelian disorders	Huntington disease Familial Creutzfeldt-Jakob disease ALS (SOD1)	Bin 3 All other loci
	Estimated number of genes/loci:	10s	10s (eventually 100s-1000s)	1000s	10s	~20,000
Alleles that would be reportable (YES) or not reportable (NO) in a clinical context
V a r i a n t s	Pathogenic	YES	YES/NO*	YES/NO*	YES/NO*	N/A^¶
	Likely pathogenic	YES	N/A^Δ	YES/NO*	YES/NO*	NO^◊
	Unknown significance (VUS)	NO	N/A^Δ	NO	NO	NO^◊
	Likely benign	NO	N/A^Δ	NO	NO	NO
	Benign	NO	NO	NO	NO	NO

Refer to UpToDate topics on genomic sequencing and disclosure of secondary findings from genetic testing for further details.

N/A: not applicable; VUS: variant of unknown significance.
* Reporting through decision making with an appropriate provider if elected by the patient.
¶ By definition, variants in genes with unknown implications could not be considered deleterious.
Δ By definition, SNPs or PGx variants will either be present or absent.
◊ Variants in genes with unknown clinical implications would not be reported; however, they may serve as an important substrate for research, potentially uncovering new disease genes.

Adapted by permission from Macmillan Publishers Ltd: Genetics in Medicine. Berg JS, Khoury MJ, Evans JP. Deploying whole genome sequencing in clinical practice and public health: Meeting the challenge one bin at a time. Genet Med 2011; 13:499. Copyright © 2011.

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Proposed system for "binning" of secondary findings from genome sequencing