20-3889097-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_153638.4(PANK2):c.-4G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000429 in 1,539,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

PANK2
NM_153638.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.67

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:

PANK2-AS1 (HGNC:40732): (PANK2 antisense RNA 1)

PANK2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 20-3889097-G-T is Benign according to our data. Variant chr20-3889097-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3051873.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000044 (61/1387678) while in subpopulation MID AF = 0.00166 (7/4218). AF 95% confidence interval is 0.000779. There are 0 homozygotes in GnomAdExome4. There are 32 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position FAILED quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
PANK2	NM_153638.4 link	c.-4G>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	NP_705902.2	Q9BZ23-1
PANK2	NM_001324192.1 link	c.-4G>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	NP_001311121.1
PANK2	NM_153638.4 link	c.-4G>T	5_prime_UTR_variant	Exon 1 of 7	NP_705902.2	Q9BZ23-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
PANK2	ENST00000316562 link	c.-4G>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	1	ENSP00000313377.4	Q9BZ23-1
PANK2	ENST00000316562 link	c.-4G>T	5_prime_UTR_variant	Exon 1 of 7	1	ENSP00000313377.4	Q9BZ23-1
PANK2	ENST00000497424.5 link	c.-246+193G>T	intron_variant	Intron 1 of 6	2	ENSP00000417609.1	Q9BZ23-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000274

AC:

AN:

145930

AF XY:

0.0000258

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.0000411

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000691

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000239

GnomAD4 exome

AF:

0.0000440

AC:

AN:

1387678

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

683420

show subpopulations

Gnomad4 AFR exome

AF:

0.0000319

AC:

AN:

31396

Gnomad4 AMR exome

AF:

0.0000566

AC:

AN:

35348

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

24456

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

35634

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

78356

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

47806

Gnomad4 NFE exome

AF:

0.0000410

AC:

AN:

1073042

Gnomad4 Remaining exome

AF:

0.000122

AC:

AN:

57422

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0000722

AC:

0.000072164

AN:

0.000072164

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000207

AC:

0.000207297

AN:

0.000207297

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00

AC:

AN:

Gnomad4 OTH

AF:

0.000473

AC:

0.000473037

AN:

0.000473037

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000453

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PANK2-related disorder

Benign:1

Mar 12, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely 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

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.8

DANN

Benign

0.73

Mutation Taster

=100/0

polymorphism

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