NM_001386393.1:c.298+557C>T

Variant names:

• chr20-3890285-C-T
• rs6084506
• NM_001386393.1:c.298+557C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386393.1(PANK2):​c.298+557C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,922 control chromosomes in the GnomAD database, including 8,516 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 0.33 (8516 hom., cov: 32)
• Consequence: PANK2 NM_001386393.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93
• Publications: 10 publications found

Genes affected

PANK2 (HGNC:15894): (pantothenate kinase 2) This gene encodes a protein belonging to the pantothenate kinase family and is the only member of that family to be expressed in mitochondria. Pantothenate kinase is a key regulatory enzyme in the biosynthesis of coenzyme A (CoA) in bacteria and mammalian cells. It catalyzes the first committed step in the universal biosynthetic pathway leading to CoA and is itself subject to regulation through feedback inhibition by acyl CoA species. Mutations in this gene are associated with HARP syndrome and pantothenate kinase-associated neurodegeneration (PKAN), formerly Hallervorden-Spatz syndrome. Alternative splicing, involving the use of alternate first exons, results in multiple transcripts encoding different isoforms. [provided by RefSeq, Jul 2008]

PANK2 Gene-Disease associations (from GenCC):

• pantothenate kinase-associated neurodegeneration

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANK2	NM_001386393.1	c.298+557C>T		intron_variant	Intron 1 of 6	ENST00000610179.7	NP_001373322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANK2	ENST00000610179.7	c.298+557C>T		intron_variant	Intron 1 of 6	1	NM_001386393.1	ENSP00000477429.2

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49399 AN: 151806 Hom.: 8519 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.325 AC: 49420 AN: 151922 Hom.: 8516 Cov.: 32 AF XY: 0.327 AC XY: 24288 AN XY: 74230

African (AFR) AF: 0.214 AC: 8880 AN: 41446

American (AMR) AF: 0.363 AC: 5540 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1114 AN: 3468

East Asian (EAS) AF: 0.338 AC: 1747 AN: 5168

South Asian (SAS) AF: 0.412 AC: 1984 AN: 4816

European-Finnish (FIN) AF: 0.348 AC: 3672 AN: 10542

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25421 AN: 67918

Other (OTH) AF: 0.343 AC: 720 AN: 2102

Alfa AF: 0.365 Hom.: 16804

Bravo AF: 0.321

Asia WGS AF: 0.387 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		2.9
PromoterAI		-0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.99
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6084506; hg19: chr20-3870932;