Variant chr22-42141910-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000433992.2(CYP2D7):c.802A>C(p.Thr268Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,610,476 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 31 hom. )

Consequence

CYP2D7
ENST00000433992.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13

Variant links:

Genes affected

CYP2D7 (HGNC:2624): (cytochrome P450 family 2 subfamily D member 7 (gene/pseudogene)) This gene is a member of the cytochrome P450 gene superfamily. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This gene is a segregating pseudogene, where some individuals may have an allele that encodes a functional enzyme, while other individuals have an allele encoding a protein that is predicted to be non-functional. In this case, the functional allele is thought to be rare. This locus is part of a cluster of cytochrome P450 genes on chromosome 22. [provided by RefSeq, Jan 2017]

CYP2D7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 22-42141910-T-G is Benign according to our data. Variant chr22-42141910-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2653243.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00225 (3276/1458314) while in subpopulation MID AF= 0.0202 (116/5754). AF 95% confidence interval is 0.0172. There are 31 homozygotes in gnomad4_exome. There are 1675 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2D7	NR_002570.6 linkuse as main transcript	n.821A>C		non_coding_transcript_exon_variant	5/9
CYP2D7	NR_145674.3 linkuse as main transcript	n.821A>C		non_coding_transcript_exon_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2D7	ENST00000433992.2 linkuse as main transcript	c.802A>C	p.Thr268Pro	missense_variant	5/9	1		P5

Frequencies

GnomAD3 genomes

AF:

0.00363

AC:

552

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00587

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.0306

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.00395

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00332

AC:

818

AN:

246470

Hom.:

AF XY:

0.00332

AC XY:

442

AN XY:

133138

show subpopulations

Gnomad AFR exome

AF:

0.00466

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.0326

Gnomad EAS exome

AF:

0.000386

Gnomad SAS exome

AF:

0.00342

Gnomad FIN exome

AF:

0.000328

Gnomad NFE exome

AF:

0.00168

Gnomad OTH exome

AF:

0.00514

GnomAD4 exome

AF:

0.00225

AC:

3276

AN:

1458314

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

1675

AN XY:

725194

show subpopulations

Gnomad4 AFR exome

AF:

0.00706

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.0317

Gnomad4 EAS exome

AF:

0.00680

Gnomad4 SAS exome

AF:

0.00277

Gnomad4 FIN exome

AF:

0.000395

Gnomad4 NFE exome

AF:

0.00106

Gnomad4 OTH exome

AF:

0.00460

GnomAD4 genome

AF:

0.00361

AC:

550

AN:

152162

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

275

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00587

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.0306

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.00395

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00852

Hom.:

Bravo

AF:

0.00393

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

CYP2D7: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.75

DANN

Benign

0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over