rs10679953

Positions:

• chr20-3916912-T-TTTCCCC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001386393.1(PANK2):​c.1083-14_1083-9dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,612,778 control chromosomes in the GnomAD database, including 15,125 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2144 hom., cov: 29)
  • Exomes 𝑓: 0.13 (12981 hom.)
• Consequence: PANK2 NM_001386393.1 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.776

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 20-3916912-T-TTTCCCC is Benign according to our data. Variant chr20-3916912-T-TTTCCCC is described in ClinVar as [Benign]. Clinvar id is 96525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PANK2	NM_001386393.1	c.1083-14_1083-9dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000610179.7	NP_001373322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PANK2	ENST00000610179.7	c.1083-14_1083-9dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001386393.1	ENSP00000477429	P2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23956 AN: 151842 Hom.: 2143 Cov.: 29

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.129 AC: 187861 AN: 1460816 Hom.: 12981 Cov.: 32 AF XY: 0.129 AC XY: 93734 AN XY: 726740

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.0918

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.0893

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.158 AC: 23971 AN: 151962 Hom.: 2144 Cov.: 29 AF XY: 0.154 AC XY: 11455 AN XY: 74308

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0858

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.165

Alfa AF: 0.149 Hom.: 298

Bravo AF: 0.166

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 09, 2018	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	May 18, 2017	- -

Pigmentary pallidal degeneration Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 02, 2013

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10679953; hg19: chr20-3897559;