rs4972842

Variant names:

• chr2-172564305-T-A
• rs4972842
• NM_002610.5:c.411-198T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002610.5(PDK1):​c.411-198T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,298 control chromosomes in the GnomAD database, including 1,563 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 0.12 (1563 hom., cov: 33)
• Consequence: PDK1 NM_002610.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 4 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=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDK1	NM_002610.5	c.411-198T>A		intron_variant	Intron 3 of 10	ENST00000282077.8	NP_002601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDK1	ENST00000282077.8	c.411-198T>A		intron_variant	Intron 3 of 10	1	NM_002610.5	ENSP00000282077.3

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18925 AN: 152180 Hom.: 1565 Cov.: 33

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0670

Gnomad FIN AF: 0.0900

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.124 AC: 18923 AN: 152298 Hom.: 1563 Cov.: 33 AF XY: 0.118 AC XY: 8768 AN XY: 74466

African (AFR) AF: 0.0374 AC: 1556 AN: 41570

American (AMR) AF: 0.155 AC: 2374 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 564 AN: 3472

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5192

South Asian (SAS) AF: 0.0656 AC: 317 AN: 4832

European-Finnish (FIN) AF: 0.0900 AC: 954 AN: 10600

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12700 AN: 68018

Other (OTH) AF: 0.128 AC: 270 AN: 2116

Alfa AF: 0.141 Hom.: 237

Bravo AF: 0.127

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.8
DANN	Benign	0.86
PhyloP100		0.13
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: rs4972842; hg19: chr2-173429033;