17-50096849-T-G

Position:

• chr17-50096849-T-G

Variant summary

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

The NM_002611.5(PDK2):​c.119-574T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,072 control chromosomes in the GnomAD database, including 11,258 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 0.38 (11258 hom., cov: 33)
• Consequence: PDK2 NM_002611.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

Genes affected

PDK2 (HGNC:8810): (pyruvate dehydrogenase kinase 2) This gene encodes a member of the pyruvate dehydrogenase kinase family. The encoded protein phosphorylates pyruvate dehydrogenase, down-regulating the activity of the mitochondrial pyruvate dehydrogenase complex. Overexpression of this gene may play a role in both cancer and diabetes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

PDK2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDK2	NM_002611.5	c.119-574T>G		intron_variant		ENST00000503176.6	NP_002602.2
PDK2	NM_001199898.2	c.-75+563T>G		intron_variant			NP_001186827.1
PDK2	NM_001199899.2	c.-74-574T>G		intron_variant			NP_001186828.1
PDK2	NM_001199900.2	c.119-574T>G		intron_variant			NP_001186829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDK2	ENST00000503176.6	c.119-574T>G		intron_variant		1	NM_002611.5	ENSP00000420927.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57885 AN: 151954 Hom.: 11258 Cov.: 33

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.381 AC: 57902 AN: 152072 Hom.: 11258 Cov.: 33 AF XY: 0.380 AC XY: 28267 AN XY: 74324

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.402

Alfa AF: 0.392 Hom.: 4802

Bravo AF: 0.386

Asia WGS AF: 0.430 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.71

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: rs4794096; hg19: chr17-48174213;