rs2743457

Variant names:

• chr22-42141242-G-A
• rs2743457
• ENST00000433992.2:c.1141C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-42141242-G-A
• chr22-42141242-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000433992.2(CYP2D7):​c.1141C>T​(p.Arg381*) 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
• Publications: 11 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000433992.2. 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
	CYP2D7	NR_002570.6		n.1103C>T		non_coding_transcript_exon	Exon 7 of 9
	CYP2D7	NR_145674.3		n.1160C>T		non_coding_transcript_exon	Exon 7 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2D7	ENST00000433992.2	TSL:1	c.1141C>T	p.Arg381*	stop_gained	Exon 7 of 9	ENSP00000439604.1
	CYP2D7	ENST00000358097.8	TSL:1	c.1084C>T	p.Arg362*	stop_gained	Exon 7 of 9	ENSP00000445124.1
	CYP2D7	ENST00000435101.2	TSL:1	n.206C>T		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.195 AC: 26862 AN: 137414 Hom.: 3168 Cov.: 27

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

GnomAD2 exomes AF: 0.0729 AC: 13780 AN: 189148 AF XY: 0.0687

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 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

African (AFR) AF: 0.202 AC: 4644 AN: 23008

American (AMR) AF: 0.112 AC: 4609 AN: 41222

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 5621 AN: 23622

East Asian (EAS) AF: 0.429 AC: 13559 AN: 31606

South Asian (SAS) AF: 0.137 AC: 10737 AN: 78500

European-Finnish (FIN) AF: 0.114 AC: 5818 AN: 51176

Middle Eastern (MID) AF: 0.127 AC: 650 AN: 5114

European-Non Finnish (NFE) AF: 0.197 AC: 188257 AN: 955028

Other (OTH) AF: 0.191 AC: 10011 AN: 52318

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

African (AFR) AF: 0.202 AC: 6756 AN: 33494

American (AMR) AF: 0.142 AC: 2022 AN: 14204

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 772 AN: 3268

East Asian (EAS) AF: 0.384 AC: 1102 AN: 2868

South Asian (SAS) AF: 0.127 AC: 557 AN: 4372

European-Finnish (FIN) AF: 0.103 AC: 1067 AN: 10316

Middle Eastern (MID) AF: 0.150 AC: 42 AN: 280

European-Non Finnish (NFE) AF: 0.212 AC: 13951 AN: 65900

Other (OTH) AF: 0.178 AC: 346 AN: 1944

Alfa AF: 0.0694 Hom.: 197

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	36
DANN	Uncertain	0.99
PhyloP100		-0.65

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

Other links and lift over

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