Genetic Variant ENST00000316562.9:c.276G>A (chr20-3889376-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000316562.9(PANK2):c.276G>A(p.Arg92Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00707 in 1,575,564 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R92R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0053 ( 18 hom., cov: 33)

Exomes 𝑓: 0.0073 ( 60 hom. )

Consequence

PANK2
ENST00000316562.9 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.33

Publications

5 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 20-3889376-G-A is Benign according to our data. Variant chr20-3889376-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 444564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.33 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00527 (803/152380) while in subpopulation NFE AF = 0.008 (544/68038). AF 95% confidence interval is 0.00744. There are 18 homozygotes in GnomAd4. There are 366 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

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	UniProt
PANK2	NM_153638.4	c.276G>A	p.Arg92Arg	synonymous	Exon 1 of 7	NP_705902.2	Q9BZ23-1
PANK2	NM_001324192.1	c.276G>A	p.Arg92Arg	synonymous	Exon 1 of 2	NP_001311121.1
PANK2	NM_024960.6	c.-246+472G>A		intron	N/A	NP_079236.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PANK2	ENST00000316562.9	TSL:1	c.276G>A	p.Arg92Arg	synonymous	Exon 1 of 7	ENSP00000313377.4	Q9BZ23-1
PANK2	ENST00000497424.5	TSL:2	c.-246+472G>A		intron	N/A	ENSP00000417609.1	Q9BZ23-2
PANK2	ENST00000495692.5	TSL:3	c.-538+360G>A		intron	N/A	ENSP00000476745.1	V9GYH1

Frequencies

GnomAD3 genomes

AF:

0.00527

AC:

803

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00799

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00352

AC:

631

AN:

179352

AF XY:

0.00330

show subpopulations

Gnomad AFR exome

AF:

0.000906

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00104

Gnomad EAS exome

AF:

0.0000762

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00684

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00726

AC:

10334

AN:

1423184

Hom.:

Cov.:

AF XY:

0.00691

AC XY:

4869

AN XY:

704950

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

32686

American (AMR)

AF:

0.00166

AC:

AN:

37958

Ashkenazi Jewish (ASJ)

AF:

0.00142

AC:

AN:

25408

East Asian (EAS)

AF:

0.00

AC:

AN:

37494

South Asian (SAS)

AF:

0.000452

AC:

AN:

81812

European-Finnish (FIN)

AF:

0.00175

AC:

AN:

49162

Middle Eastern (MID)

AF:

0.00105

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00884

AC:

9675

AN:

1094008

Other (OTH)

AF:

0.00662

AC:

390

AN:

58940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

727

1455

2182

2910

3637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.00527

AC:

803

AN:

152380

Hom.:

Cov.:

AF XY:

0.00491

AC XY:

366

AN XY:

74516

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

41600

American (AMR)

AF:

0.00209

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00800

AC:

544

AN:

68038

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

127

169

211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00621

Hom.:

Bravo

AF:

0.00556

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (6)

not specified (2)

Pigmentary pallidal degeneration (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

1.3

PromoterAI

0.028

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over