NM_002610.5:c.1056+1638T>C

Variant names:

• chr2-172588026-T-C
• rs6710129
• NM_002610.5:c.1056+1638T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002610.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDK1	NM_002610.5	MANE Select	c.1056+1638T>C		intron	N/A	NP_002601.1
	PDK1	NM_001278549.2		c.1116+1638T>C		intron	N/A	NP_001265478.1
	PDK1	NR_103729.2		n.1117+1638T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDK1	ENST00000282077.8	TSL:1 MANE Select	c.1056+1638T>C		intron	N/A	ENSP00000282077.3
	PDK1	ENST00000392571.6	TSL:1	c.1116+1638T>C		intron	N/A	ENSP00000376352.2
	PDK1	ENST00000410055.5	TSL:1	c.1056+1638T>C		intron	N/A	ENSP00000386985.1

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

African (AFR) AF: 0.489 AC: 20290 AN: 41484

American (AMR) AF: 0.240 AC: 3665 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3472

East Asian (EAS) AF: 0.231 AC: 1197 AN: 5186

South Asian (SAS) AF: 0.220 AC: 1063 AN: 4822

European-Finnish (FIN) AF: 0.147 AC: 1559 AN: 10594

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12261 AN: 67998

Other (OTH) AF: 0.244 AC: 516 AN: 2112

Alfa AF: 0.130 Hom.: 313

Bravo AF: 0.288

Asia WGS AF: 0.258 AC: 897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.23
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6710129; hg19: chr2-173452754;