Variant 17-50097549-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002611.5(PDK2):c.245A>T(p.Gln82Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PDK2
NM_002611.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.24

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3498252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PDK2	NM_002611.5 linkuse as main transcript	c.245A>T	p.Gln82Leu	missense_variant	2/11	ENST00000503176.6	NP_002602.2
PDK2	NM_001199898.2 linkuse as main transcript	c.53A>T	p.Gln18Leu	missense_variant	3/12		NP_001186827.1
PDK2	NM_001199899.2 linkuse as main transcript	c.53A>T	p.Gln18Leu	missense_variant	2/11		NP_001186828.1
PDK2	NM_001199900.2 linkuse as main transcript	c.245A>T	p.Gln82Leu	missense_variant	2/4		NP_001186829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDK2	ENST00000503176.6 linkuse as main transcript	c.245A>T	p.Gln82Leu	missense_variant	2/11	1	NM_002611.5	ENSP00000420927	P1	Q15119-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461068

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2023

The c.245A>T (p.Q82L) alteration is located in exon 2 (coding exon 2) of the PDK2 gene. This alteration results from a A to T substitution at nucleotide position 245, causing the glutamine (Q) at amino acid position 82 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.59

.;.;D;T;T;.;.

Eigen

Benign

0.039

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

.;D;T;D;D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.35

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

.;.;L;.;.;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-4.0

D;D;D;D;D;.;D

REVEL

Benign

0.091

Sift

Benign

0.13

T;T;T;T;T;.;T

Sift4G

Benign

0.40

T;T;T;T;T;T;T

Polyphen

0.29

.;.;B;.;.;.;.

Vest4

0.66

MutPred

0.54

.;.;Loss of loop (P = 0.0986);.;.;.;.;

MVP

0.42

MPC

0.78

ClinPred

0.90

GERP RS

4.1

Varity_R

0.48

gMVP

0.60

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over