rs10679953

Variant names:

• chr20-3916912-T-TTTCCCC
• rs10679953
• NM_001386393.1:c.1083-14_1083-9dupTTCCCC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001386393.1(PANK2):​c.1083-14_1083-9dupTTCCCC variant causes a splice region, 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_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.776
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• pantothenate kinase-associated neurodegeneration

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PANK2	NM_001386393.1	c.1083-14_1083-9dupTTCCCC		splice_region_variant, intron_variant	Intron 4 of 6	ENST00000610179.7	NP_001373322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANK2	ENST00000610179.7	c.1083-15_1083-14insTTCCCC		intron_variant	Intron 4 of 6	1	NM_001386393.1	ENSP00000477429.2

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

African (AFR) AF: 0.252 AC: 8409 AN: 33426

American (AMR) AF: 0.0918 AC: 4103 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 3976 AN: 26118

East Asian (EAS) AF: 0.169 AC: 6698 AN: 39682

South Asian (SAS) AF: 0.128 AC: 11016 AN: 86214

European-Finnish (FIN) AF: 0.0893 AC: 4770 AN: 53396

Middle Eastern (MID) AF: 0.206 AC: 1188 AN: 5764

European-Non Finnish (NFE) AF: 0.125 AC: 139247 AN: 1111172

Other (OTH) AF: 0.140 AC: 8454 AN: 60350

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

African (AFR) AF: 0.243 AC: 10059 AN: 41388

American (AMR) AF: 0.127 AC: 1942 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3468

East Asian (EAS) AF: 0.165 AC: 849 AN: 5160

South Asian (SAS) AF: 0.125 AC: 602 AN: 4810

European-Finnish (FIN) AF: 0.0858 AC: 909 AN: 10592

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8633 AN: 67958

Other (OTH) AF: 0.165 AC: 347 AN: 2106

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

May 18, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pigmentary pallidal degeneration Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Oct 02, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10679953; hg19: chr20-3897559;