NM_001386393.1(PANK2):c.1094T>C (p.Met365Thr) AND Pigmentary pallidal degeneration

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 17, 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:: RCV003064597.3

Allele description [Variation Report for NM_001386393.1(PANK2):c.1094T>C (p.Met365Thr)]

NM_001386393.1(PANK2):c.1094T>C (p.Met365Thr)

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.1094T>C (p.Met365Thr)

HGVS:

NC_000020.11:g.3916938T>C
NG_008131.3:g.33100T>C
NM_001324191.2:c.551T>C
NM_001324193.2:c.116T>C
NM_001386393.1:c.1094T>CMANE SELECT
NM_024960.6:c.551T>C
NM_153638.4:c.1424T>C
NM_153640.4:c.551T>C
NP_001311120.1:p.Met184Thr
NP_001311122.1:p.Met39Thr
NP_001373322.1:p.Met365Thr
NP_079236.3:p.Met184Thr
NP_705902.2:p.Met475Thr
NP_705904.1:p.Met184Thr
LRG_1016t1:c.1424T>C
LRG_1016t2:c.1094T>C
LRG_1016:g.33100T>C
LRG_1016p1:p.Met475Thr
LRG_1016p2:p.Met365Thr
NC_000020.10:g.3897585T>C
NR_136715.2:n.995T>C

Protein change:

M184T

Molecular consequence:

NM_001324191.2:c.551T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001324193.2:c.116T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001386393.1:c.1094T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024960.6:c.551T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_153638.4:c.1424T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_153640.4:c.551T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_136715.2:n.995T>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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cytochrome oxidase subunit 1, partial (mitochondrion) [Megaspilidae sp. BIOUG303...
cytochrome oxidase subunit 1, partial (mitochondrion) [Megaspilidae sp. BIOUG30395-A04]
gi|1491941259|gb|AYK40844.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003443410	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 17, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28781879, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003443410

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 17, 2022)

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

Novel PANK2 mutation in the first Greek compound heterozygote patient with pantothenate-kinase-associated neurodegeneration.

Paraskevas GP, Yapijakis C, Bougea A, Constantinides V, Bourbouli M, Stamboulis E, Kapaki E.

SAGE Open Med Case Rep. 2017;5:2050313X17720101. doi: 10.1177/2050313X17720101.

PubMed [citation]

PMID:: 28781879
PMCID:: PMC5521331

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, SCV003443410.2

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

Description

For these reasons, this variant has been classified as 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 missense change has been observed in individual(s) with clinical features of PANK2-related conditions (PMID: 28781879). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 475 of the PANK2 protein (p.Met475Thr).

#	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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