chr17-50108622-G-C

Variant names:

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

Variant summary

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

The NM_002611.5(PDK2):​c.872G>C​(p.Arg291Pro) 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: 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: 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>C	p.Arg291Pro	missense_variant	Exon 9 of 11	ENST00000503176.6	NP_002602.2
PDK2	NM_001199898.2	c.680G>C	p.Arg227Pro	missense_variant	Exon 10 of 12		NP_001186827.1
PDK2	NM_001199899.2	c.680G>C	p.Arg227Pro	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>C	p.Arg291Pro	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	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	.;D;T;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.74	.;T;T;T
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	2.9	.;M;.;.
PhyloP100		4.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.6	D;D;D;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.014	D;D;D;.
Sift4G	Uncertain	0.029	D;D;D;D
Polyphen		0.25	.;B;.;.
Vest4		0.75
MutPred		0.54		.;Loss of MoRF binding (P = 0.003);.;.;
MVP		0.67
MPC		1.6
ClinPred		0.97	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.88
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;