20-3889480-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001386393.1(PANK2):c.50G>T(p.Gly17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000809 in 1,493,912 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00082 ( 13 hom. )

Consequence

PANK2
NM_001386393.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.08

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008071929).

BP6

Variant 20-3889480-G-T is Benign according to our data. Variant chr20-3889480-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 285843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-3889480-G-T is described in Lovd as [Benign]. Variant chr20-3889480-G-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00067 (102/152318) while in subpopulation SAS AF= 0.00952 (46/4830). AF 95% confidence interval is 0.00734. There are 0 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANK2	NM_001386393.1 link	c.50G>T	p.Gly17Val	missense_variant	Exon 1 of 7	ENST00000610179.7	NP_001373322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANK2	ENST00000610179.7 link	c.50G>T	p.Gly17Val	missense_variant	Exon 1 of 7	1	NM_001386393.1	ENSP00000477429.2		Q9BZ23-4

Frequencies

GnomAD3 genomes

AF:

0.000657

AC:

100

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00931

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00173

AC:

167

AN:

96748

Hom.:

AF XY:

0.00204

AC XY:

111

AN XY:

54466

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000297

Gnomad ASJ exome

AF:

0.00114

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00795

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000697

Gnomad OTH exome

AF:

0.00176

GnomAD4 exome

AF:

0.000824

AC:

1106

AN:

1341594

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

684

AN XY:

660158

show subpopulations

Gnomad4 AFR exome

AF:

0.000177

Gnomad4 AMR exome

AF:

0.000289

Gnomad4 ASJ exome

AF:

0.000505

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00829

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000368

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.000670

AC:

102

AN:

152318

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00952

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000505

Hom.:

Bravo

AF:

0.000487

ExAC

AF:

0.00153

AC:

158

Asia WGS

AF:

0.00260

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pigmentary pallidal degeneration

Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Jun 01, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Has not been previously published as pathogenic or benign to our knowledge In silico analysis supports that this missense variant does not alter protein structure/function -

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PANK2: PP3, BS2 -

not specified

Benign:1

Jan 29, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PANK2-related disorder

Benign:1

Aug 07, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;.

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.80

T;T

MetaRNN

Benign

0.0081

T;T

MetaSVM

Uncertain

0.76

MutationAssessor

Benign

0.0

N;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.51

N;.

REVEL

Uncertain

0.46

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.020

D;D

Polyphen

0.61

P;.

Vest4

0.43

MVP

0.98

MPC

0.62

ClinPred

0.083

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over