rs28371706

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.320C>T(p.Thr107Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,609,412 control chromosomes in the GnomAD database, including 2,087 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign,other (★★).

Frequency

Genomes: 𝑓 0.052 ( 1019 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 1068 hom. )

Consequence

CYP2D6
NM_000106.6 missense

Scores

Clinical Significance

Likely benign; other criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -2.91

Publications

219 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=0.0049679875).

BP6

Variant 22-42129770-G-A is Benign according to our data. Variant chr22-42129770-G-A is described in ClinVar as Likely_benign|other. ClinVar VariationId is 39379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2D6	NM_000106.6	MANE Select	c.320C>T	p.Thr107Ile	missense	Exon 2 of 9	NP_000097.3
	CYP2D6	NM_001025161.3		c.320C>T	p.Thr107Ile	missense	Exon 2 of 8	NP_001020332.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CYP2D6	ENST00000645361.2	MANE Select	c.320C>T	p.Thr107Ile	missense	Exon 2 of 9	ENSP00000496150.1
CYP2D6	ENST00000359033.4	TSL:1	c.320C>T	p.Thr107Ile	missense	Exon 2 of 8	ENSP00000351927.4
CYP2D6	ENST00000360124.10	TSL:1	n.320C>T		non_coding_transcript_exon	Exon 2 of 8	ENSP00000353241.6

Frequencies

GnomAD3 genomes

AF:

0.0518

AC:

7830

AN:

151262

Hom.:

1010

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0142

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.0379

GnomAD2 exomes

AF:

0.0141

AC:

3431

AN:

244170

AF XY:

0.0109

show subpopulations

Gnomad AFR exome

AF:

0.185

Gnomad AMR exome

AF:

0.00717

Gnomad ASJ exome

AF:

0.0182

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000191

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.00799

GnomAD4 exome

AF:

0.00619

AC:

9031

AN:

1458040

Hom.:

1068

Cov.:

AF XY:

0.00544

AC XY:

3948

AN XY:

725406

show subpopulations

African (AFR)

AF:

0.196

AC:

6532

AN:

33334

American (AMR)

AF:

0.00920

AC:

410

AN:

44564

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

436

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39590

South Asian (SAS)

AF:

0.00115

AC:

AN:

86118

European-Finnish (FIN)

AF:

0.000192

AC:

AN:

52118

Middle Eastern (MID)

AF:

0.0226

AC:

130

AN:

5764

European-Non Finnish (NFE)

AF:

0.000599

AC:

665

AN:

1110216

Other (OTH)

AF:

0.0124

AC:

749

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

430

860

1290

1720

2150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

206

412

618

824

1030

<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:

0.0519

AC:

7849

AN:

151372

Hom.:

1019

Cov.:

AF XY:

0.0496

AC XY:

3672

AN XY:

73974

show subpopulations

African (AFR)

AF:

0.181

AC:

7405

AN:

40968

American (AMR)

AF:

0.0142

AC:

216

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00125

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00114

AC:

AN:

67840

Other (OTH)

AF:

0.0375

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

262

523

785

1046

1308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0483

Hom.:

356

Bravo

AF:

0.0583

ESP6500AA

AF:

0.169

AC:

741

ESP6500EA

AF:

0.00175

AC:

ExAC

AF:

0.0178

AC:

2149

EpiCase

AF:

0.00186

EpiControl

AF:

0.00190

ClinVar

ClinVar submissions as Germline

Significance:Likely benign; other

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.0060

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.00096

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.055

MetaRNN

Benign

0.0050

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.070

PhyloP100

-2.9

PrimateAI

Benign

0.46

PROVEAN

Benign

0.41

REVEL

Benign

0.092

Sift

Benign

0.31

Sift4G

Benign

0.24

Vest4

0.069

MPC

0.12

ClinPred

0.0065

GERP RS

-1.7

Varity_R

0.16

gMVP

0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over