NM_017990.5:c.1754+87G>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017990.5(PDPR):​c.1754+87G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000758 in 1,319,750 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 51)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 51

GnomAD4 exome AF: 7.58e-7 AC: 1 AN: 1319750 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 655478

African (AFR) AF: 0.00 AC: 0 AN: 29684

American (AMR) AF: 0.00 AC: 0 AN: 33302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22584

East Asian (EAS) AF: 0.00 AC: 0 AN: 37046

South Asian (SAS) AF: 0.00 AC: 0 AN: 74926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5336

European-Non Finnish (NFE) AF: 9.89e-7 AC: 1 AN: 1010734

Other (OTH) AF: 0.00 AC: 0 AN: 55012

GnomAD4 genome Cov.: 51

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		0.17

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;