rs6710129

Positions:

• chr2-172588026-T-C
• chr2-172588026-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002610.5(PDK1):​c.1056+1638T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,154 control chromosomes in the GnomAD database, including 7,061 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (7061 hom., cov: 32)
• Consequence: PDK1 NM_002610.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999

Genes affected

PDK1 (HGNC:8809): (pyruvate dehydrogenase kinase 1) Pyruvate dehydrogenase (PDH) is a mitochondrial multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate and is one of the major enzymes responsible for the regulation of homeostasis of carbohydrate fuels in mammals. The enzymatic activity is regulated by a phosphorylation/dephosphorylation cycle. Phosphorylation of PDH by a specific pyruvate dehydrogenase kinase (PDK) results in inactivation. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDK1	NM_002610.5	c.1056+1638T>C		intron_variant		ENST00000282077.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDK1	ENST00000282077.8	c.1056+1638T>C		intron_variant		1	NM_002610.5	P1
PDK1	ENST00000392571.6	c.1116+1638T>C		intron_variant		1
PDK1	ENST00000410055.5	c.1056+1638T>C		intron_variant		1		P1
PDK1	ENST00000466437.1	n.351+1638T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41237 AN: 152036 Hom.: 7038 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.272 AC: 41318 AN: 152154 Hom.: 7061 Cov.: 32 AF XY: 0.269 AC XY: 20029 AN XY: 74390

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.244

Alfa AF: 0.112 Hom.: 218

Bravo AF: 0.288

Asia WGS AF: 0.258 AC: 897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.23

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

LitVar

Other links and lift over

dbSNP: rs6710129; hg19: chr2-173452754;