rs28371725

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000106.6(CYP2D6):c.985+39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 1,606,516 control chromosomes in the GnomAD database, including 11,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign,drug response,other (★★).

Frequency

Genomes: 𝑓 0.070 ( 775 hom., cov: 32)

Exomes 𝑓: 0.094 ( 10990 hom. )

Consequence

CYP2D6
NM_000106.6 intron

Scores

Clinical Significance

Likely benign; drug response; other criteria provided, multiple submitters, no conflicts B:1O:4

Conservation

PhyloP100: -0.879

Publications

301 publications found

Variant links:

Genes affected

CYP2D6 (HGNC:2625): (cytochrome P450 family 2 subfamily D member 6) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize as many as 25% of commonly prescribed drugs. Its substrates include antidepressants, antipsychotics, analgesics and antitussives, beta adrenergic blocking agents, antiarrythmics and antiemetics. The gene is highly polymorphic in the human population; certain alleles result in the poor metabolizer phenotype, characterized by a decreased ability to metabolize the enzyme's substrates. Some individuals with the poor metabolizer phenotype have no functional protein since they carry 2 null alleles whereas in other individuals the gene is absent. This gene can vary in copy number and individuals with the ultrarapid metabolizer phenotype can have 3 or more active copies of the gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

CYP2D6 links:

NDUFA6-DT (HGNC:45273): (NDUFA6 divergent transcript)

NDUFA6-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015609562).

BP6

Variant 22-42127803-C-T is Benign according to our data. Variant chr22-42127803-C-T is described in ClinVar as Likely_benign|drug_response|other. ClinVar VariationId is 39381.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000106.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2D6	NM_000106.6	MANE Select	c.985+39G>A		intron	N/A	NP_000097.3
	CYP2D6	NM_001025161.3		c.832+39G>A		intron	N/A	NP_001020332.2	P10635-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYP2D6	ENST00000645361.2	MANE Select	c.985+39G>A	intron	N/A	ENSP00000496150.1	P10635-1
CYP2D6	ENST00000359033.4	TSL:1	c.832+39G>A	intron	N/A	ENSP00000351927.4	P10635-2
CYP2D6	ENST00000360124.10	TSL:1	n.*60+39G>A	intron	N/A	ENSP00000353241.6	H7BY38

Frequencies

GnomAD3 genomes

AF:

0.0697

AC:

10540

AN:

151116

Hom.:

778

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0260

Gnomad AMI

AF:

0.0773

Gnomad AMR

AF:

0.0662

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.0330

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.0301

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.0955

Gnomad OTH

AF:

0.0841

GnomAD2 exomes

AF:

0.0807

AC:

20150

AN:

249596

AF XY:

0.0864

show subpopulations

Gnomad AFR exome

AF:

0.0276

Gnomad AMR exome

AF:

0.0399

Gnomad ASJ exome

AF:

0.176

Gnomad EAS exome

AF:

0.0321

Gnomad FIN exome

AF:

0.0320

Gnomad NFE exome

AF:

0.0938

Gnomad OTH exome

AF:

0.0962

GnomAD4 exome

AF:

0.0939

AC:

136709

AN:

1455284

Hom.:

10990

Cov.:

AF XY:

0.0960

AC XY:

69497

AN XY:

724264

show subpopulations

African (AFR)

AF:

0.0262

AC:

872

AN:

33230

American (AMR)

AF:

0.0444

AC:

1982

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

4675

AN:

26104

East Asian (EAS)

AF:

0.0214

AC:

845

AN:

39578

South Asian (SAS)

AF:

0.136

AC:

11689

AN:

86036

European-Finnish (FIN)

AF:

0.0323

AC:

1723

AN:

53372

Middle Eastern (MID)

AF:

0.151

AC:

869

AN:

5756

European-Non Finnish (NFE)

AF:

0.0975

AC:

107857

AN:

1106396

Other (OTH)

AF:

0.103

AC:

6197

AN:

60148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

6894

13788

20682

27576

34470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3852

7704

11556

15408

19260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0697

AC:

10534

AN:

151232

Hom.:

775

Cov.:

AF XY:

0.0679

AC XY:

5015

AN XY:

73910

show subpopulations

African (AFR)

AF:

0.0260

AC:

1068

AN:

41050

American (AMR)

AF:

0.0662

AC:

1006

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

621

AN:

3466

East Asian (EAS)

AF:

0.0321

AC:

165

AN:

5134

South Asian (SAS)

AF:

0.126

AC:

603

AN:

4770

European-Finnish (FIN)

AF:

0.0301

AC:

319

AN:

10606

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0955

AC:

6466

AN:

67710

Other (OTH)

AF:

0.0833

AC:

174

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

457

913

1370

1826

2283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0681

Hom.:

290

Bravo

AF:

0.0703

TwinsUK

AF:

0.0947

AC:

351

ALSPAC

AF:

0.0996

AC:

384

ESP6500AA

AF:

0.0337

AC:

148

ESP6500EA

AF:

0.100

AC:

859

ExAC

AF:

0.0806

AC:

9777

Asia WGS

AF:

0.0780

AC:

270

AN:

3466

ClinVar

ClinVar submissions

Significance:Likely benign; drug response; other

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Deutetrabenazine response (1)

Tamoxifen response (1)

Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.7

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0081

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.18

MetaRNN

Benign

0.0016

PhyloP100

-0.88

Sift4G

Benign

0.42

Vest4

0.18

GERP RS

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over