XR_001738772.3:n.1486+32327A>G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDK1	XR_001738772.3	n.1486+32327A>G		intron_variant	Intron 12 of 13
PDK1	XR_001738774.3	n.1426+32327A>G		intron_variant	Intron 11 of 11
PDK1	XR_007076394.1	n.1486+32327A>G		intron_variant	Intron 12 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	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

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.838

Gnomad4 EAS AF: 0.980

Gnomad4 SAS AF: 0.756

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.774

Alfa AF: 0.797 Hom.: 25732

Bravo AF: 0.755

Asia WGS AF: 0.840 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs836589; hg19: chr2-173493078;