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NM_001386393.1(PANK2):c.1255A>G (p.Ile419Val) AND Pigmentary pallidal degeneration

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 11, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000796153.9

Allele description [Variation Report for NM_001386393.1(PANK2):c.1255A>G (p.Ile419Val)]

NM_001386393.1(PANK2):c.1255A>G (p.Ile419Val)

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.1255A>G (p.Ile419Val)
Other names:
p.Ile529Val
HGVS:
  • NC_000020.11:g.3918719A>G
  • NG_008131.3:g.34881A>G
  • NM_001324191.2:c.712A>G
  • NM_001324193.2:c.277A>G
  • NM_001386393.1:c.1255A>GMANE SELECT
  • NM_024960.6:c.712A>G
  • NM_153638.3:c.1585A>G
  • NM_153638.4:c.1585A>G
  • NM_153640.4:c.712A>G
  • NP_001311120.1:p.Ile238Val
  • NP_001311122.1:p.Ile93Val
  • NP_001373322.1:p.Ile419Val
  • NP_079236.3:p.Ile238Val
  • NP_705902.2:p.Ile529Val
  • NP_705904.1:p.Ile238Val
  • LRG_1016t1:c.1585A>G
  • LRG_1016t2:c.1255A>G
  • LRG_1016:g.34881A>G
  • LRG_1016p1:p.Ile529Val
  • LRG_1016p2:p.Ile419Val
  • NC_000020.10:g.3899366A>G
  • NM_153638.2:c.1585A>G
  • NR_136715.2:n.1156A>G
Protein change:
I238V
Links:
dbSNP: rs761156912
NCBI 1000 Genomes Browser:
rs761156912
Molecular consequence:
  • NM_001324191.2:c.712A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001324193.2:c.277A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386393.1:c.1255A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_024960.6:c.712A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153638.4:c.1585A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153640.4:c.712A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136715.2:n.1156A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000935651Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 11, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Neuro-ophthalmologic and electroretinographic findings in pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz syndrome).

Egan RA, Weleber RG, Hogarth P, Gregory A, Coryell J, Westaway SK, Gitschier J, Das S, Hayflick SJ.

Am J Ophthalmol. 2005 Aug;140(2):267-74.

PubMed [citation]
PMID:
16023068
PMCID:
PMC2169522

Partial deficit of pantothenate kinase 2 catalytic activity in a case of tremor-predominant neurodegeneration with brain iron accumulation.

Liang TW, Truax AC, Trojanowski JQ, Lee VM, Stern MB, Kotzbauer PT.

Mov Disord. 2006 May;21(5):718-22.

PubMed [citation]
PMID:
16450344
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000935651.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 529 of the PANK2 protein (p.Ile529Val). This variant is present in population databases (rs761156912, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of pantothenate kinase-associated neurodegeneration (PMID: 16023068, 16450344; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 642654). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PANK2 protein function. Experimental studies have shown that this missense change does not substantially affect PANK2 function (PMID: 16450344). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 30, 2024