NM_001386393.1(PANK2):c.1184C>A (p.Ala395Glu) AND Pigmentary pallidal degeneration

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 26, 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:: RCV003502048.2

Allele description [Variation Report for NM_001386393.1(PANK2):c.1184C>A (p.Ala395Glu)]

NM_001386393.1(PANK2):c.1184C>A (p.Ala395Glu)

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.1184C>A (p.Ala395Glu)

HGVS:

NC_000020.11:g.3917028C>A
NG_008131.3:g.33190C>A
NM_001324191.2:c.641C>A
NM_001324193.2:c.206C>A
NM_001386393.1:c.1184C>AMANE SELECT
NM_024960.6:c.641C>A
NM_153638.4:c.1514C>A
NM_153640.4:c.641C>A
NP_001311120.1:p.Ala214Glu
NP_001311122.1:p.Ala69Glu
NP_001373322.1:p.Ala395Glu
NP_079236.3:p.Ala214Glu
NP_705902.2:p.Ala505Glu
NP_705904.1:p.Ala214Glu
LRG_1016t1:c.1514C>A
LRG_1016t2:c.1184C>A
LRG_1016:g.33190C>A
LRG_1016p1:p.Ala505Glu
LRG_1016p2:p.Ala395Glu
NC_000020.10:g.3897675C>A
NR_136715.2:n.1085C>A

Protein change:

A214E

Molecular consequence:

NM_001324191.2:c.641C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001324193.2:c.206C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001386393.1:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024960.6:c.641C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_153638.4:c.1514C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_153640.4:c.641C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_136715.2:n.1085C>A - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004298027	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Apr 26, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16962235, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004298027

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Apr 26, 2023)

germline

clinical testing

PubMed (2)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

PANK2 gene analysis confirms genetic heterogeneity in neurodegeneration with brain iron accumulation (NBIA) but mutations are rare in other types of adult neurodegenerative disease.

Matarin MM, Singleton AB, Houlden H.

Neurosci Lett. 2006 Oct 23;407(2):162-5. Epub 2006 Sep 7.

PubMed [citation]

PMID:: 16962235

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004298027.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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) performed at Invitae indicates that this missense variant is expected to disrupt PANK2 protein function. This variant is also known as p.Ala395Glu. This missense change has been observed in individual(s) with neurodegeneration with brain iron accumulation (PMID: 16962235). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 505 of the PANK2 protein (p.Ala505Glu).

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine