rs11686903

Positions:

• chr2-172581558-C-T

Variant summary

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

The NM_002610.5(PDK1):​c.946-4720C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,120 control chromosomes in the GnomAD database, including 5,605 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 0.24 (5605 hom., cov: 33)
• Consequence: PDK1 NM_002610.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDK1	NM_002610.5	c.946-4720C>T		intron_variant		ENST00000282077.8	NP_002601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDK1	ENST00000282077.8	c.946-4720C>T		intron_variant		1	NM_002610.5	ENSP00000282077	P1
PDK1	ENST00000392571.6	c.1006-4720C>T		intron_variant		1		ENSP00000376352
PDK1	ENST00000410055.5	c.946-4720C>T		intron_variant		1		ENSP00000386985	P1
PDK1	ENST00000466437.1	n.241-4720C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36621 AN: 152004 Hom.: 5611 Cov.: 33

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.262

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.241 AC: 36610 AN: 152120 Hom.: 5605 Cov.: 33 AF XY: 0.238 AC XY: 17725 AN XY: 74360

Gnomad4 AFR AF: 0.0806

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.258

Alfa AF: 0.298 Hom.: 2823

Bravo AF: 0.218

Asia WGS AF: 0.100 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.77

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: rs11686903; hg19: chr2-173446286;