chr17-50097430-C-T

Variant names:

• chr17-50097430-C-T
• rs11546968
• NM_002611.5:c.126C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_002611.5(PDK2):​c.126C>T​(p.Ser42Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,613,758 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (1 hom.)
• Consequence: PDK2 NM_002611.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.354
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 17-50097430-C-T is Benign according to our data. Variant chr17-50097430-C-T is described in ClinVar as [Benign]. Clinvar id is 791201.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.354 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDK2	NM_002611.5	c.126C>T	p.Ser42Ser	synonymous_variant	Exon 2 of 11	ENST00000503176.6	NP_002602.2
PDK2	NM_001199900.2	c.126C>T	p.Ser42Ser	synonymous_variant	Exon 2 of 4		NP_001186829.1
PDK2	NM_001199898.2	c.-67C>T		5_prime_UTR_variant	Exon 3 of 12		NP_001186827.1
PDK2	NM_001199899.2	c.-67C>T		5_prime_UTR_variant	Exon 2 of 11		NP_001186828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDK2	ENST00000503176.6	c.126C>T	p.Ser42Ser	synonymous_variant	Exon 2 of 11	1	NM_002611.5	ENSP00000420927.1

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 597 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.00133 AC: 334 AN: 251024 AF XY: 0.00116

Gnomad AFR exome AF: 0.0127

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000537

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.000735 AC: 1074 AN: 1461486 Hom.: 1 Cov.: 31 AF XY: 0.000701 AC XY: 510 AN XY: 727064

African (AFR) AF: 0.0125 AC: 418 AN: 33478

American (AMR) AF: 0.00163 AC: 73 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53096

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.000431 AC: 479 AN: 1111962

Other (OTH) AF: 0.00136 AC: 82 AN: 60392

GnomAD4 genome AF: 0.00392 AC: 597 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.00367 AC XY: 273 AN XY: 74450

African (AFR) AF: 0.0123 AC: 510 AN: 41552

American (AMR) AF: 0.00301 AC: 46 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68018

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.00212 Hom.: 1

Bravo AF: 0.00460

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.74
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=277/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs11546968; hg19: chr17-48174794;