NM_001386393.1(PANK2):c.519C>A (p.His173Gln) AND Pigmentary pallidal degeneration

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 15, 2022
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:: RCV001991576.4

Allele description [Variation Report for NM_001386393.1(PANK2):c.519C>A (p.His173Gln)]

NM_001386393.1(PANK2):c.519C>A (p.His173Gln)

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.519C>A (p.His173Gln)

HGVS:

NC_000020.11:g.3908146C>A
NG_008131.3:g.24308C>A
NM_001324191.2:c.-25C>A
NM_001324192.1:c.849C>A
NM_001324193.2:c.-328+11C>A
NM_001386393.1:c.519C>AMANE SELECT
NM_024960.6:c.-25C>A
NM_153638.4:c.849C>A
NM_153640.4:c.-25C>A
NP_001311121.1:p.His283Gln
NP_001373322.1:p.His173Gln
NP_705902.2:p.His283Gln
LRG_1016t1:c.849C>A
LRG_1016t2:c.519C>A
LRG_1016:g.24308C>A
LRG_1016p1:p.His283Gln
LRG_1016p2:p.His173Gln
NC_000020.10:g.3888793C>A

Protein change:

H173Q

Links:

dbSNP: rs2090416889

NCBI 1000 Genomes Browser:

rs2090416889

Molecular consequence:

NM_001324191.2:c.-25C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_024960.6:c.-25C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_153640.4:c.-25C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001324193.2:c.-328+11C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001324192.1:c.849C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001386393.1:c.519C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_153638.4:c.849C>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002282135	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 15, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22416811, 16157712, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002282135

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 15, 2022)

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

Pantothenate kinase-associated neurodegeneration is not a synucleinopathy.

Li A, Paudel R, Johnson R, Courtney R, Lees AJ, Holton JL, Hardy J, Revesz T, Houlden H.

Neuropathol Appl Neurobiol. 2013 Feb;39(2):121-31. doi: 10.1111/j.1365-2990.2012.01269.x.

PubMed [citation]

PMID:: 22416811
PMCID:: PMC3712463

A novel mutation in a patient with pantothenate kinase-associated neurodegeneration.

Saleheen D, Nazir A, Khanum S, Haider SR, Frossard P.

CMAJ. 2005 Sep 13;173(6):578-9. No abstract available.

PubMed [citation]

PMID:: 16157712
PMCID:: PMC1197146

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002282135.3

#	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 histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 283 of the PANK2 protein (p.His283Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with pantothenate kinase-associated neurodegeneration (PMID: 22416811). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.His283 amino acid residue in PANK2. Other variant(s) that disrupt this residue have been observed in individuals with PANK2-related conditions (PMID: 16157712), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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