2-172628350-A-G

Variant names:

• chr2-172628350-A-G
• rs836589
• XR_001738772.3:n.1486+32327A>G

Variant summary

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

The XR_001738772.3(PDK1):​n.1486+32327A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,212 control chromosomes in the GnomAD database, including 44,935 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 0.76 (44935 hom., cov: 33)
• Consequence: PDK1 XR_001738772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 15 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115643 AN: 152094 Hom.: 44912 Cov.: 33

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.760 AC: 115709 AN: 152212 Hom.: 44935 Cov.: 33 AF XY: 0.764 AC XY: 56879 AN XY: 74404

African (AFR) AF: 0.594 AC: 24656 AN: 41504

American (AMR) AF: 0.840 AC: 12844 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2908 AN: 3472

East Asian (EAS) AF: 0.980 AC: 5067 AN: 5172

South Asian (SAS) AF: 0.756 AC: 3652 AN: 4828

European-Finnish (FIN) AF: 0.850 AC: 9015 AN: 10602

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55064 AN: 68020

Other (OTH) AF: 0.774 AC: 1635 AN: 2112

Alfa AF: 0.777 Hom.: 55206

Bravo AF: 0.755

Asia WGS AF: 0.840 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.99
DANN	Benign	0.29
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs836589; hg19: chr2-173493078;