2-172597502-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002610.5(PDK1):c.*1533G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,156 control chromosomes in the GnomAD database, including 3,710 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3710 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: PDK1 NM_002610.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

Genes affected

PDK1 (HGNC:8809): (pyruvate dehydrogenase kinase 1) Pyruvate dehydrogenase (PDH) is a mitochondrial multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate and is one of the major enzymes responsible for the regulation of homeostasis of carbohydrate fuels in mammals. The enzymatic activity is regulated by a phosphorylation/dephosphorylation cycle. Phosphorylation of PDH by a specific pyruvate dehydrogenase kinase (PDK) results in inactivation. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDK1	NM_002610.5	c.*1533G>T		3_prime_UTR_variant	11/11	ENST00000282077.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDK1	ENST00000282077.8	c.*1533G>T		3_prime_UTR_variant	11/11	1	NM_002610.5	P1
PDK1	ENST00000410055.5	c.*55-111G>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29641 AN: 152030 Hom.: 3703 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.195 AC: 29689 AN: 152148 Hom.: 3710 Cov.: 32 AF XY: 0.192 AC XY: 14266 AN XY: 74374

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0197

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.183

Alfa AF: 0.149 Hom.: 1860

Bravo AF: 0.202

Asia WGS AF: 0.129 AC: 449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.2
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11904366; hg19: chr2-173462230;