NM_001386393.1(PANK2):c.1021C>T (p.Arg341Ter) AND Pigmentary pallidal degeneration

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 25, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000826147.8

Allele description [Variation Report for NM_001386393.1(PANK2):c.1021C>T (p.Arg341Ter)]

NM_001386393.1(PANK2):c.1021C>T (p.Arg341Ter)

Gene:

PANK2:pantothenate kinase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20p13

Genomic location:

Preferred name:

NM_001386393.1(PANK2):c.1021C>T (p.Arg341Ter)

Other names:

1021C>T; Arg341Ter

HGVS:

NC_000020.11:g.3912573C>T
NG_008131.3:g.28735C>T
NM_001324191.2:c.478C>T
NM_001324193.2:c.43C>T
NM_001386393.1:c.1021C>TMANE SELECT
NM_024960.6:c.478C>T
NM_153638.4:c.1351C>T
NM_153640.4:c.478C>T
NP_001311120.1:p.Arg160Ter
NP_001311122.1:p.Arg15Ter
NP_001373322.1:p.Arg341Ter
NP_079236.3:p.Arg160Ter
NP_705902.2:p.Arg451Ter
NP_705904.1:p.Arg160Ter
LRG_1016t1:c.1351C>T
LRG_1016t2:c.1021C>T
LRG_1016:g.28735C>T
LRG_1016p1:p.Arg451Ter
LRG_1016p2:p.Arg341Ter
NC_000020.10:g.3893220C>T
NM_153638.2:c.1351C>T
NR_136715.2:n.922C>T
p.Arg451X

Protein change:

R15*

Links:

dbSNP: rs1250997630

NCBI 1000 Genomes Browser:

rs1250997630

Molecular consequence:

NR_136715.2:n.922C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001324191.2:c.478C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324193.2:c.43C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386393.1:c.1021C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_024960.6:c.478C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_153638.4:c.1351C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_153640.4:c.478C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Pigmentary pallidal degeneration (NBIA1)
Synonyms:: PKAN NEUROAXONAL DYSTROPHY, JUVENILE-ONSET; Pantothenate kinase-associated neurodegeneration; Neuroaxonal dystrophy, late infantile; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009319; MedGen: C0018523; Orphanet: 157850; OMIM: 234200

Recent activity

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Homo sapiens calcium voltage-gated channel auxiliary subunit gamma 6 (CACNG6), t...
Homo sapiens calcium voltage-gated channel auxiliary subunit gamma 6 (CACNG6), transcript variant 1, mRNA
gi|1862723009|ref|NM_145814.2|

Nucleotide
Fejervarya kupitzi voucher CAS 210276 small subunit ribosomal RNA gene, partial ...
Fejervarya kupitzi voucher CAS 210276 small subunit ribosomal RNA gene, partial sequence; mitochondrial
gi|1590714907|gb|MK621384.1|

Nucleotide
spike glycoprotein [Pipistrellus bat coronavirus HKU5]
spike glycoprotein [Pipistrellus bat coronavirus HKU5]
gi|520688503|gb|AGP04932.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000967678	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Nov 12, 2018)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 11479594, 24209433, 24348190, 21480873, 26828213, 22103354, 12510040, 15911822, 24033266
SCV002014769	GeneReviews	no classification provided	not provided	germline	literature only
SCV004298020	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 25, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12510040, 11479594, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000967678

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Nov 12, 2018)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

SCV002014769

GeneReviews

no classification provided

not provided

germline

literature only

SCV004298020

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 25, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, literature only

Citations

PubMed

Pantothenate kinase-associated neurodegeneration (PKAN) and PLA2G6-associated neurodegeneration (PLAN): review of two major neurodegeneration with brain iron accumulation (NBIA) phenotypes.

Kurian MA, Hayflick SJ.

Int Rev Neurobiol. 2013;110:49-71. doi: 10.1016/B978-0-12-410502-7.00003-X. Review.

PubMed [citation]

PMID:: 24209433
PMCID:: PMC6059649

Phenotypes and genotypes of patients with pantothenate kinase-associated neurodegeneration in Asian and Caucasian populations: 2 cases and literature review.

Lee CH, Lu CS, Chuang WL, Yeh TH, Jung SM, Huang CL, Lai SC.

ScientificWorldJournal. 2013;2013:860539. doi: 10.1155/2013/860539. Review.

PubMed [citation]

PMID:: 24348190
PMCID:: PMC3854131

See all PubMed Citations (10)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967678.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (9)

Description

The p.Arg451X variant in PANK2 has been reported in the homozygous or compound h eterozygous state in at least 5 individuals with features of pantothenate kinase -associated neurodegeneration (PKAN; Zhou 2001, Hayflick 2003, Pellecchia 2012, Lim 2012, Bijarnia-Mahay 2013, Udani 2016). It has also been identified in 0.007 % (2/30616) of South Asian chromosomes by the Genome Aggregation Database (gnomA D, http://gnomad.broadinstitute.org); however this frequency is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 451, which is predicted to lead to a tr uncated or absent protein. Loss of function of the PANK2 gene is an established disease mechanism in autosomal recessive PKAN. In summary, this variant meets cr iteria to be classified as pathogenic for autosomal recessive PKAN. ACMG/AMP Cri teria applied: PVS1, PM2, PM3

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		1	not provided	1	not provided

From GeneReviews, SCV002014769.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004298020.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg451*) in the PANK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PANK2 are known to be pathogenic (PMID: 11479594, 12510040). This variant is present in population databases (no rsID available, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with neurodegeneration with brain iron accumulation (PMID: 11479594). This variant is also known as R341X. ClinVar contains an entry for this variant (Variation ID: 667397). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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