NM_001386393.1(PANK2):c.944T>C (p.Leu315Pro) 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:: RCV001935746.4

Allele description [Variation Report for NM_001386393.1(PANK2):c.944T>C (p.Leu315Pro)]

NM_001386393.1(PANK2):c.944T>C (p.Leu315Pro)

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.944T>C (p.Leu315Pro)

HGVS:

NC_000020.11:g.3912496T>C
NG_008131.3:g.28658T>C
NM_001324191.2:c.401T>C
NM_001324193.2:c.-35T>C
NM_001386393.1:c.944T>CMANE SELECT
NM_024960.6:c.401T>C
NM_153638.4:c.1274T>C
NM_153640.4:c.401T>C
NP_001311120.1:p.Leu134Pro
NP_001373322.1:p.Leu315Pro
NP_079236.3:p.Leu134Pro
NP_705902.2:p.Leu425Pro
NP_705904.1:p.Leu134Pro
LRG_1016t1:c.1274T>C
LRG_1016t2:c.944T>C
LRG_1016:g.28658T>C
LRG_1016p1:p.Leu425Pro
LRG_1016p2:p.Leu315Pro
NC_000020.10:g.3893143T>C
NR_136715.2:n.845T>C

Protein change:

L134P

Links:

dbSNP: rs2146872522

NCBI 1000 Genomes Browser:

rs2146872522

Molecular consequence:

NM_001324193.2:c.-35T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001324191.2:c.401T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001386393.1:c.944T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024960.6:c.401T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_153638.4:c.1274T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_153640.4:c.401T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_136715.2:n.845T>C - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002195568	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 11, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16437574, 18006953, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002195568

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 11, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation.

Hartig MB, Hörtnagel K, Garavaglia B, Zorzi G, Kmiec T, Klopstock T, Rostasy K, Svetel M, Kostic VS, Schuelke M, Botz E, Weindl A, Novakovic I, Nardocci N, Prokisch H, Meitinger T.

Ann Neurol. 2006 Feb;59(2):248-56.

PubMed [citation]

PMID:: 16437574

A novel PANK2 gene mutation: clinical and molecular characteristics of patients short communication.

Kazek B, Jamroz E, Gencik M, Jezela Stanek A, Marszal E, Wojaczynska-Stanek K.

J Child Neurol. 2007 Nov;22(11):1256-9.

PubMed [citation]

PMID:: 18006953

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002195568.3

#	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 replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 425 of the PANK2 protein (p.Leu425Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of neurodegeneration with brain iron accumulation (PMID: 16437574; Invitae). ClinVar contains an entry for this variant (Variation ID: 1416528). 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 with a positive predictive value of 95%. This variant disrupts the p.Leu425 amino acid residue in PANK2. Other variant(s) that disrupt this residue have been observed in individuals with PANK2-related conditions (PMID: 16437574, 18006953), which suggests that this may be a clinically significant amino acid residue. 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: Sep 29, 2024

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