chr20-3889376-G-A

Position:

chr20-3889376-G-A

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

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]

PANK2 links:

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
PANK2	NM_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
PANK2	ENST00000610179.7 linkuse as main transcript			upstream_gene_variant		1	NM_001386393.1	ENSP00000477429	P2	Q9BZ23-4

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

GnomAD3 exomes

AF:

0.00352

AC:

631

AN:

179352

Hom.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00556

Asia WGS

AF:

0.000577

AC:

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 provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 23, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	PANK2: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 11, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 15, 2017	- -

Pigmentary pallidal degeneration

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This 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 submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

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.

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