Submissions for variant CYP2D6*10

gnomAD frequency: 0.18675  dbSNP: rs1065852

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000603460	SCV000730663	likely benign	not specified	2018-03-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Eurofins Ntd Llc (ga)	RCV000734607	SCV000862761	other	not provided	2018-08-06	criteria provided, single submitter	clinical testing
Medical Genetics Summaries	RCV001030444	SCV001193762	drug response	Deutetrabenazine response	2019-05-01	criteria provided, single submitter	curation	CYP2D6*10 has decreased function: individuals with one decreased function and one no function allele (e.g., *4/*10) are intermediate metabolizers; individuals with two decreased function alleles (e.g. *10/*10) are normal metabolizers or intermediate metabolizers (controversy remains). Therapeutic recommendations from professional societies state that the maximum dose of deutetrabenazine should not exceed 36 mg per day in individuals with 2 decreased function alleles (CYP2D6 poor metabolizers) to avoid abnormally high plasma levels due to reduced metabolic clearance.
Medical Genetics Summaries	RCV001093717	SCV001250912	drug response	Tamoxifen response	2019-05-01	criteria provided, single submitter	curation	CYP2D6*10 has decreased function: individuals with one decreased function and one no function allele (e.g., *4/*10) are intermediate metabolizers; individuals with two decreased function alleles (e.g. *10/*10) are normal metabolizers or intermediate metabolizers (controversy remains). Therapeutic recommendations from professional societies state that intermediate metabolizers may benefit less from tamoxifen therapy because they have lower concentrations of tamoxifen's major active metabolite, endoxifin, compared with normal metabolizers. For tamoxifen, CPIC prescribing recommendations for individuals with an activity score (AS) of 1.0 are allele dependent, based on the presence of the *10 allele: if a *10 allele is present, individuals are provided a 'moderate' recommendation; if *10 is NOT present, individuals are graded as 'optional' because the recommendations are primarily extrapolated from evidence generated from *10 individuals (i.e., limited data for clinical outcomes and pharmacokinetics for this group).
OMIM	RCV000018389	SCV000038671	drug response	Debrisoquine, poor metabolism of	2023-08-08	no assertion criteria provided	literature only
Bruce Budowle Laboratory, University of North Texas Health Science Center	RCV001029560	SCV001192346	drug response	Tramadol response	2018-04-28	no assertion criteria provided	research