17-50096849-T-G

Variant names:

• chr17-50096849-T-G
• rs4794096
• NM_002611.5:c.119-574T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PDK2	NM_002611.5	c.119-574T>G		intron_variant	Intron 1 of 10	ENST00000503176.6	NP_002602.2
PDK2	NM_001199898.2	c.-75+563T>G		intron_variant	Intron 2 of 11		NP_001186827.1
PDK2	NM_001199899.2	c.-74-574T>G		intron_variant	Intron 1 of 10		NP_001186828.1
PDK2	NM_001199900.2	c.119-574T>G		intron_variant	Intron 1 of 3		NP_001186829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDK2	ENST00000503176.6	c.119-574T>G		intron_variant	Intron 1 of 10	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

African (AFR) AF: 0.316 AC: 13099 AN: 41470

American (AMR) AF: 0.417 AC: 6379 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1882 AN: 3468

East Asian (EAS) AF: 0.566 AC: 2927 AN: 5168

South Asian (SAS) AF: 0.316 AC: 1523 AN: 4826

European-Finnish (FIN) AF: 0.381 AC: 4025 AN: 10572

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26701 AN: 67964

Other (OTH) AF: 0.402 AC: 850 AN: 2114

Alfa AF: 0.391 Hom.: 21166

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
PhyloP100		0.28
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: rs4794096; hg19: chr17-48174213;