rs2743457

chr22-42141242-G-Achr22-42141242-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4 BS2

The ENST00000433992.2(CYP2D7):c.1141C>T(p.Arg381Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.20 (3167 hom., cov: 27)
  • Exomes 𝑓: 0.19 (29750 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP2D7 ENST00000433992.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM4: Stoplost variant in ENST00000433992.2 Downstream stopcodon found after 46 codons.
• BS2: High Homozygotes in GnomAdExome at 3655 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2D7	NR_002570.6	n.1103C>T		non_coding_transcript_exon_variant	7/9
CYP2D7	NR_145674.3	n.1160C>T		non_coding_transcript_exon_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2D7	ENST00000433992.2	c.1141C>T	p.Arg381Ter	stop_gained	7/9	1		P5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 26862 AN: 137414 Hom.: 3168 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.182

GnomAD3 exomes AF: 0.0729 AC: 13780 AN: 189148 Hom.: 3655 AF XY: 0.0687 AC XY: 7040 AN XY: 102490

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.0474

Gnomad ASJ exome AF: 0.0848

Gnomad EAS exome AF: 0.449

Gnomad SAS exome AF: 0.0384

Gnomad FIN exome AF: 0.00981

Gnomad NFE exome AF: 0.0461

Gnomad OTH exome AF: 0.0625

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.193 AC: 243906 AN: 1261594 Hom.: 29750 Cov.: 25 AF XY: 0.192 AC XY: 121621 AN XY: 633026

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.195 AC: 26867 AN: 137522 Hom.: 3167 Cov.: 27 AF XY: 0.187 AC XY: 12505 AN XY: 66960

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.178

Alfa AF: 0.0694 Hom.: 197

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
Cadd	Pathogenic	36
Dann	Uncertain	0.99

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

Other links and lift over

dbSNP: rs2743457; hg19: chr22-42537252; COSMIC: COSV63851834; COSMIC: COSV63851834;