rs11686903

Variant names:

• chr2-172581558-C-T
• rs11686903
• NM_002610.5:c.946-4720C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002610.5. 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
	PDK1	NM_002610.5	MANE Select	c.946-4720C>T		intron	N/A	NP_002601.1	Q15118-1
	PDK1	NM_001278549.2		c.1006-4720C>T		intron	N/A	NP_001265478.1	Q15118-2
	PDK1	NR_103729.2		n.1007-4720C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDK1	ENST00000282077.8	TSL:1 MANE Select	c.946-4720C>T		intron	N/A	ENSP00000282077.3	Q15118-1
	PDK1	ENST00000392571.6	TSL:1	c.1006-4720C>T		intron	N/A	ENSP00000376352.2	Q15118-2
	PDK1	ENST00000410055.5	TSL:1	c.946-4720C>T		intron	N/A	ENSP00000386985.1	Q15118-1

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

African (AFR) AF: 0.0806 AC: 3346 AN: 41514

American (AMR) AF: 0.200 AC: 3056 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1112 AN: 3470

East Asian (EAS) AF: 0.0133 AC: 69 AN: 5180

South Asian (SAS) AF: 0.154 AC: 742 AN: 4826

European-Finnish (FIN) AF: 0.353 AC: 3723 AN: 10540

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.348 AC: 23637 AN: 67984

Other (OTH) AF: 0.258 AC: 545 AN: 2110

Alfa AF: 0.310 Hom.: 14496

Bravo AF: 0.218

Asia WGS AF: 0.100 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.77
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs11686903; hg19: chr2-173446286;