20-3889237-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The ENST00000316562.9(PANK2):c.137A>G(p.Asp46Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D46V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PANK2
ENST00000316562.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.871

Publications

9 publications found

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: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 41 curated pathogenic missense variants (we use a threshold of 10). The gene has 11 curated benign missense variants. Gene score misZ: 0.17856 (below the threshold of 3.09). Trascript score misZ: -1.1034 (below the threshold of 3.09). GenCC associations: The gene is linked to pantothenate kinase-associated neurodegeneration.

BP4

Computational evidence support a benign effect (MetaRNN=0.042028874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000316562.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein
PANK2	NM_153638.4	c.137A>G	p.Asp46Gly	missense	Exon 1 of 7	NP_705902.2
PANK2	NM_001324192.1	c.137A>G	p.Asp46Gly	missense	Exon 1 of 2	NP_001311121.1
PANK2	NM_024960.6	c.-246+333A>G		intron	N/A	NP_079236.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PANK2	ENST00000316562.9	TSL:1	c.137A>G	p.Asp46Gly	missense	Exon 1 of 7	ENSP00000313377.4
PANK2	ENST00000497424.5	TSL:2	c.-246+333A>G		intron	N/A	ENSP00000417609.1
PANK2	ENST00000495692.5	TSL:3	c.-538+221A>G		intron	N/A	ENSP00000476745.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460980

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726656

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26096

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

85898

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111722

Other (OTH)

AF:

0.00

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.0069

BayesDel_noAF

Benign

-0.25

CADD

Benign

3.6

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.18

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.24

M_CAP

Benign

0.085

MetaRNN

Benign

0.042

MetaSVM

Uncertain

0.037

MutationAssessor

Benign

0.0

PhyloP100

-0.87

PrimateAI

Benign

0.39

PROVEAN

Benign

0.42

REVEL

Benign

0.16

Sift

Benign

1.0

Sift4G

Benign

0.81

Polyphen

0.0

Vest4

0.092

MutPred

0.17

Gain of sheet (P = 0.0266)

MVP

0.64

MPC

0.59

ClinPred

0.087

GERP RS

-3.8

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.034

gMVP

0.021

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over