rs142832849

Variant names:

• chr20-3889376-G-A
• rs142832849
• ENST00000316562.9:c.276G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-3889376-G-A
• chr20-3889376-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 1.33
• 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-AS1 (HGNC:40732): (PANK2 antisense RNA 1)

ACMG classification

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANK2	NM_001386393.1	c.-55G>A		upstream_gene_variant		ENST00000610179.7	NP_001373322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANK2	ENST00000610179.7	c.-55G>A		upstream_gene_variant		1	NM_001386393.1	ENSP00000477429.2

Frequencies

GnomAD3 genomes AF: 0.00527 AC: 803 AN: 152262 Hom.: 18 Cov.: 33

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

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.: 60 Cov.: 31 AF XY: 0.00691 AC XY: 4869 AN XY: 704950

African (AFR) AF: 0.00125 AC: 41 AN: 32686

American (AMR) AF: 0.00166 AC: 63 AN: 37958

Ashkenazi Jewish (ASJ) AF: 0.00142 AC: 36 AN: 25408

East Asian (EAS) AF: 0.00 AC: 0 AN: 37494

South Asian (SAS) AF: 0.000452 AC: 37 AN: 81812

European-Finnish (FIN) AF: 0.00175 AC: 86 AN: 49162

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5716

European-Non Finnish (NFE) AF: 0.00884 AC: 9675 AN: 1094008

Other (OTH) AF: 0.00662 AC: 390 AN: 58940

GnomAD4 genome AF: 0.00527 AC: 803 AN: 152380 Hom.: 18 Cov.: 33 AF XY: 0.00491 AC XY: 366 AN XY: 74516

African (AFR) AF: 0.00137 AC: 57 AN: 41600

American (AMR) AF: 0.00209 AC: 32 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00800 AC: 544 AN: 68038

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00621 Hom.: 17

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

Submissions by phenotype

not provided Benign:6

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 23, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PANK2: BP4, BP7, BS2 -

not specified Benign:2

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 15, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pigmentary pallidal degeneration Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Uncertain	0.98
PhyloP100		1.3
PromoterAI		0.028	Neutral
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs142832849; hg19: chr20-3870023;