NM_002611.5:c.119-574T>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002611.5(PDK2):​c.119-574T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002611.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDK2	NM_002611.5	MANE Select	c.119-574T>C		intron	N/A	NP_002602.2
	PDK2	NM_001199898.2		c.-75+563T>C		intron	N/A	NP_001186827.1	Q15119-2
	PDK2	NM_001199899.2		c.-74-574T>C		intron	N/A	NP_001186828.1	Q15119-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDK2	ENST00000503176.6	TSL:1 MANE Select	c.119-574T>C		intron	N/A	ENSP00000420927.1	Q15119-1
	PDK2	ENST00000892669.1		c.119-574T>C		intron	N/A	ENSP00000562728.1
	PDK2	ENST00000892667.1		c.119-574T>C		intron	N/A	ENSP00000562726.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.72
PhyloP100		0.28

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;