VCV000016895.2 - ClinVar

NM_000106.5(CYP2D6):c.[886C>T;457G>C]

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

drug response

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This haplotype includes the following variants

NM_000106.5(CYP2D6):c.[886C>T;457G>C]

Other names: CYP2D6, ARG296CYS AND SER486THR
CYP2D6*2
Functional consequence: -
Links: ClinGen: CA039192; OMIM: 124030.0007

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CYP2D6		-	-	GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh37	245	336

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Debrisoquine, ultrarapid metabolism of	drug response (1)	no assertion criteria provided	May 18, 2015	RCV000018391.36

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
drug response (May 18, 2015)	no assertion criteria provided Method: literature only	DEBRISOQUINE, ULTRARAPID METABOLISM OF Affected status: not provided Allele origin: germline	OMIM Accession: SCV000038673.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (2) PubMed: 7903454‚ 7927337 Comment on evidence: This allelic variant is also known as CYP2D62 or CYP2D6L. In a family in which 2 sibs and their father had MRs of less that … (more) This allelic variant is also known as CYP2D62 or CYP2D6L. In a family in which 2 sibs and their father had MRs of less that 0.02 (ultrarapid phenotype, see 608902), Johansson et al. (1993) found 12 extra copies of the CYP2D6 gene inherited in an autosomal dominant pattern; in a second family in which 2 sibs had MRs of less than 0.1, the authors found 2 extra copies of the CYP2D6 gene. All affected individuals had a variant CYP2D6 gene, termed CYP2D6L, which contained 2 amino acid substitutions: a 2938C-T transition in exon 6, resulting in an arg296-to-cys (R296C), and a 4268G-to-C transversion in exon 9, resulting in a resulting in a ser486-to-thr (S486T) substitution. The MR of individuals with 1 copy of the CYP2D6L gene did not differ from those with the wildtype gene, but there was a correlation between decreased MR and increased copies of the CYP2D6L gene. Panserat et al. (1994) identified the R296C and S486T changes as 2 major CYP2D6 allozymes in extensive metabolizers (wildtype). Residue 296 falls within a presumed substrate recognition site, and residue 486 lies in the vicinity of the heme binding site. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
DNA haplotype-dependent differences in the amino acid sequence of debrisoquine 4-hydroxylase (CYP2D6): evidence for two major allozymes in extensive metabolisers.	Panserat S	Human genetics	1994	PMID: 7927337
Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine.	Johansson I	Proceedings of the National Academy of Sciences of the United States of America	1993	PMID: 7903454
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP2D6	-	-	-	-

Text-mined citations for this variant ...

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000106.5(CYP2D6):c.[886C>T;457G>C]

Variant Details

NM_000106.5(CYP2D6):c.[886C>T;457G>C]

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...