17-50108622-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_002611.5(PDK2):c.872G>A(p.Arg291Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000493 in 1,611,360 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00094 ( 5 hom., cov: 31)
Exomes 𝑓: 0.00045 ( 0 hom. )
Consequence
PDK2
NM_002611.5 missense
NM_002611.5 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 4.01
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.015206218).
BS2
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PDK2 | NM_002611.5 | c.872G>A | p.Arg291Gln | missense_variant | 9/11 | ENST00000503176.6 | NP_002602.2 | |
PDK2 | NM_001199898.2 | c.680G>A | p.Arg227Gln | missense_variant | 10/12 | NP_001186827.1 | ||
PDK2 | NM_001199899.2 | c.680G>A | p.Arg227Gln | missense_variant | 9/11 | NP_001186828.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PDK2 | ENST00000503176.6 | c.872G>A | p.Arg291Gln | missense_variant | 9/11 | 1 | NM_002611.5 | ENSP00000420927 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000940 AC: 143AN: 152086Hom.: 5 Cov.: 31
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GnomAD3 exomes AF: 0.000291 AC: 72AN: 247568Hom.: 0 AF XY: 0.000352 AC XY: 47AN XY: 133684
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GnomAD4 exome AF: 0.000446 AC: 651AN: 1459274Hom.: 0 Cov.: 32 AF XY: 0.000402 AC XY: 292AN XY: 725710
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GnomAD4 genome AF: 0.000940 AC: 143AN: 152086Hom.: 5 Cov.: 31 AF XY: 0.000969 AC XY: 72AN XY: 74294
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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 | Aug 09, 2021 | The c.872G>A (p.R291Q) alteration is located in exon 9 (coding exon 9) of the PDK2 gene. This alteration results from a G to A substitution at nucleotide position 872, causing the arginine (R) at amino acid position 291 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.
REVEL
Benign
Sift
Benign
T;T;T;.
Sift4G
Benign
T;T;T;T
Polyphen
0.15
.;B;.;.
Vest4
MVP
MPC
0.65
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at