rs2303200

Variant names:

• chr16-70143745-G-A
• rs2303200
• NM_017990.5:c.1754+87G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 6 publications found

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]

ENSG00000247228 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDPR	NM_017990.5	c.1754+87G>A		intron_variant	Intron 14 of 18	ENST00000288050.9	NP_060460.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDPR	ENST00000288050.9	c.1754+87G>A		intron_variant	Intron 14 of 18	1	NM_017990.5	ENSP00000288050.5

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98261 AN: 150916 Hom.: 23106 Cov.: 51

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

African (AFR) AF: 0.686 AC: 20278 AN: 29576

American (AMR) AF: 0.676 AC: 22286 AN: 32986

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 13682 AN: 22346

East Asian (EAS) AF: 0.753 AC: 27881 AN: 37026

South Asian (SAS) AF: 0.661 AC: 49137 AN: 74302

European-Finnish (FIN) AF: 0.613 AC: 31026 AN: 50624

Middle Eastern (MID) AF: 0.612 AC: 3238 AN: 5290

European-Non Finnish (NFE) AF: 0.594 AC: 588035 AN: 989488

Other (OTH) AF: 0.616 AC: 33435 AN: 54246

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

African (AFR) AF: 0.700 AC: 28982 AN: 41422

American (AMR) AF: 0.678 AC: 10287 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2167 AN: 3450

East Asian (EAS) AF: 0.760 AC: 3925 AN: 5166

South Asian (SAS) AF: 0.687 AC: 3305 AN: 4808

European-Finnish (FIN) AF: 0.615 AC: 6454 AN: 10486

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.611 AC: 41088 AN: 67230

Other (OTH) AF: 0.646 AC: 1356 AN: 2100

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
PhyloP100		0.17
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: rs2303200; hg19: chr16-70177648; COSMIC: COSV55355353; COSMIC: COSV55355353;