22-42130547-T-C

Position:

• chr22-42130547-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_000106.6(CYP2D6):​c.180+65A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.083 (928 hom., cov: 23)
  • Exomes 𝑓: 0.13 (24548 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP2D6 NM_000106.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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]

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

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=1.554).
• BP6: Variant 22-42130547-T-C is Benign according to our data. Variant chr22-42130547-T-C is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2D6	NM_000106.6	c.180+65A>G		intron_variant		ENST00000645361.2	NP_000097.3
CYP2D6	NM_001025161.3	c.180+65A>G		intron_variant			NP_001020332.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2D6	ENST00000645361.2	c.180+65A>G		intron_variant			NM_000106.6	ENSP00000496150	P1
NDUFA6-DT	ENST00000439129.5	n.1718+5140T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 8119 AN: 97292 Hom.: 925 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.0432

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0201

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.0904

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.108

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.128 AC: 111101 AN: 871158 Hom.: 24548 Cov.: 20 AF XY: 0.132 AC XY: 57248 AN XY: 433644

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.247

Gnomad4 EAS exome AF: 0.0344

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.148

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0835 AC: 8127 AN: 97364 Hom.: 928 Cov.: 23 AF XY: 0.0825 AC XY: 3892 AN XY: 47156

Gnomad4 AFR AF: 0.0790

Gnomad4 AMR AF: 0.0853

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0199

Gnomad4 SAS AF: 0.0935

Gnomad4 FIN AF: 0.0904

Gnomad4 NFE AF: 0.0866

Gnomad4 OTH AF: 0.107

Alfa AF: 0.293 Hom.: 1041

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	1.6

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1081000; hg19: -;