chr17-50108622-G-T

Variant names:

• chr17-50108622-G-T
• rs148586321
• NM_002611.5:c.872G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002611.5(PDK2):​c.872G>T​(p.Arg291Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R291Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PDK2 NM_002611.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDK2	NM_002611.5	c.872G>T	p.Arg291Leu	missense_variant	Exon 9 of 11	ENST00000503176.6	NP_002602.2
PDK2	NM_001199898.2	c.680G>T	p.Arg227Leu	missense_variant	Exon 10 of 12		NP_001186827.1
PDK2	NM_001199899.2	c.680G>T	p.Arg227Leu	missense_variant	Exon 9 of 11		NP_001186828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDK2	ENST00000503176.6	c.872G>T	p.Arg291Leu	missense_variant	Exon 9 of 11	1	NM_002611.5	ENSP00000420927.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.62	.;D;T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	.;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	.;L;.;.
PhyloP100		4.0
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-4.5	D;D;D;.
REVEL	Benign	0.17
Sift	Benign	0.28	T;T;T;.
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.010	.;B;.;.
Vest4		0.70
MutPred		0.61		.;Loss of MoRF binding (P = 0.008);.;.;
MVP		0.61
MPC		0.88
ClinPred		0.90	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.41
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs148586321; hg19: chr17-48185986;