rs142832849

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000316562.9(PANK2):​c.276G>A​(p.Arg92=) 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 (★★).

Frequency

Genomes: 𝑓 0.0053 ( 18 hom., cov: 33)
Exomes 𝑓: 0.0073 ( 60 hom. )

Consequence

PANK2
ENST00000316562.9 synonymous

Scores

1
1

Clinical Significance

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

Conservation

PhyloP100: 1.33
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 444564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-3889376-G-A is described in Lovd as [Benign]. Variant chr20-3889376-G-A is described in Lovd as [Likely_benign].
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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 18 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PANK2NM_001386393.1 linkuse as main transcript upstream_gene_variant ENST00000610179.7 NP_001373322.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PANK2ENST00000610179.7 linkuse as main transcript upstream_gene_variant 1 NM_001386393.1 ENSP00000477429 P2Q9BZ23-4

Frequencies

GnomAD3 genomes
AF:
0.00527
AC:
803
AN:
152262
Hom.:
18
Cov.:
33
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
GnomAD3 exomes
AF:
0.00352
AC:
631
AN:
179352
Hom.:
2
AF XY:
0.00330
AC XY:
321
AN XY:
97374
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 SAS exome
AF:
0.000476
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.:
60
Cov.:
31
AF XY:
0.00691
AC XY:
4869
AN XY:
704950
show subpopulations
Gnomad4 AFR exome
AF:
0.00125
Gnomad4 AMR exome
AF:
0.00166
Gnomad4 ASJ exome
AF:
0.00142
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000452
Gnomad4 FIN exome
AF:
0.00175
Gnomad4 NFE exome
AF:
0.00884
Gnomad4 OTH exome
AF:
0.00662
GnomAD4 genome
AF:
0.00527
AC:
803
AN:
152380
Hom.:
18
Cov.:
33
AF XY:
0.00491
AC XY:
366
AN XY:
74516
show subpopulations
Gnomad4 AFR
AF:
0.00137
Gnomad4 AMR
AF:
0.00209
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00245
Gnomad4 NFE
AF:
0.00800
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00701
Hom.:
7
Bravo
AF:
0.00556
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:6
Likely benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Likely benign, no assertion criteria providedclinical testingMayo Clinic Laboratories, Mayo ClinicFeb 23, 2016- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2024PANK2: BP4, BP7, BS2 -
Benign, criteria provided, single submitterclinical testingGeneDxJan 11, 2019- -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:2
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsFeb 15, 2017- -
Pigmentary pallidal degeneration Benign:2
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
CADD
Benign
17
DANN
Uncertain
0.98

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.

Other links and lift over

dbSNP: rs142832849; hg19: chr20-3870023; API