rs2303200

Positions:

• chr16-70143745-G-A
• chr16-70143745-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017990.5(PDPR):​c.1754+87G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.65 (23138 hom., cov: 51)
  • Exomes 𝑓: 0.61 (146041 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDPR NM_017990.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

Genes affected

PDPR (HGNC:30264): (pyruvate dehydrogenase phosphatase regulatory subunit) Pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate and links glycolysis to the tricarboxylic acid cycle and fatty acid synthesis. The dephosphorylation and reactivation of PDC is catalyzed by pyruvate dehydrogenase phosphatase (PDP). The dimeric PDP has a catalytic subunit and a regulatory subunit. This gene encodes the FAD-containing regulatory subunit of PDP. The encoded protein acts to decrease the sensitivity of the PDP catalytic subunit to magnesium ions. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDPR	NM_017990.5	c.1754+87G>A		intron_variant		ENST00000288050.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDPR	ENST00000288050.9	c.1754+87G>A		intron_variant		1	NM_017990.5	P1
	ENST00000671539.1	n.892-4509C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 98261 AN: 150916 Hom.: 23106 Cov.: 51 FAILED QC

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.648

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.609 AC: 788998 AN: 1295884 Hom.: 146041 AF XY: 0.610 AC XY: 392994 AN XY: 643844

Gnomad4 AFR exome AF: 0.686

Gnomad4 AMR exome AF: 0.676

Gnomad4 ASJ exome AF: 0.612

Gnomad4 EAS exome AF: 0.753

Gnomad4 SAS exome AF: 0.661

Gnomad4 FIN exome AF: 0.613

Gnomad4 NFE exome AF: 0.594

Gnomad4 OTH exome AF: 0.616

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.651 AC: 98353 AN: 151036 Hom.: 23138 Cov.: 51 AF XY: 0.654 AC XY: 48277 AN XY: 73868

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.646

Alfa AF: 0.637 Hom.: 2348

Asia WGS AF: 0.742 AC: 2582 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	4.3
DANN	Benign	0.73

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: rs2303200; hg19: chr16-70177648; COSMIC: COSV55355353; COSMIC: COSV55355353;