NM_001386393.1(PANK2):c.189_201del (p.Ala64fs) AND Pigmentary pallidal degeneration

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 9, 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:: RCV003613234.2

Allele description [Variation Report for NM_001386393.1(PANK2):c.189_201del (p.Ala64fs)]

NM_001386393.1(PANK2):c.189_201del (p.Ala64fs)

Genes:

LOC130065345:ATAC-STARR-seq lymphoblastoid silent region 12635 [Gene]
PANK2:pantothenate kinase 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

20p13

Genomic location:

Preferred name:

NM_001386393.1(PANK2):c.189_201del (p.Ala64fs)

HGVS:

NC_000020.11:g.3889619_3889631del
NG_008131.3:g.5781_5793del
NG_199762.1:g.448_460del
NM_001324191.2:c.-523_-511del
NM_001324192.1:c.519_531del
NM_001386393.1:c.189_201delMANE SELECT
NM_024960.6:c.-246+715_-246+727del
NM_153638.4:c.519_531del
NP_001311121.1:p.Ala174fs
NP_001373322.1:p.Ala64fs
NP_705902.2:p.Ala174fs
LRG_1016t1:c.519_531del
LRG_1016t2:c.189_201del
LRG_1016:g.5781_5793del
LRG_1016p1:p.Ala174fs
LRG_1016p2:p.Ala64fs
NC_000020.10:g.3870263_3870275del
NC_000020.10:g.3870266_3870278del
NR_136715.2:n.233_245del

Protein change:

A174fs

Molecular consequence:

NM_001324191.2:c.-523_-511del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001324192.1:c.519_531del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386393.1:c.189_201del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_153638.4:c.519_531del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024960.6:c.-246+715_-246+727del - intron variant - [Sequence Ontology: SO:0001627]
NR_136715.2:n.233_245del - 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
SCV004504448	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 9, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11479594, 12510040, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004504448

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 9, 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

A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.

Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J, Hayflick SJ.

Nat Genet. 2001 Aug;28(4):345-9.

PubMed [citation]

PMID:: 11479594

Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome.

Hayflick SJ, Westaway SK, Levinson B, Zhou B, Johnson MA, Ching KH, Gitschier J.

N Engl J Med. 2003 Jan 2;348(1):33-40.

PubMed [citation]

PMID:: 12510040

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004504448.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PANK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala174Argfs*27) in the PANK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PANK2 are known to be pathogenic (PMID: 11479594, 12510040).

#	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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