NM_000533.5(PLP1):c.142_152del (p.Glu48fs) AND Hereditary spastic paraplegia 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 28, 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:: RCV002622394.3

Allele description [Variation Report for NM_000533.5(PLP1):c.142_152del (p.Glu48fs)]

NM_000533.5(PLP1):c.142_152del (p.Glu48fs)

Genes:

RAB9B:RAB9B, member RAS oncogene family [Gene - OMIM - HGNC]
PLP1:proteolipid protein 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xq22.2

Genomic location:

Preferred name:

NM_000533.5(PLP1):c.142_152del (p.Glu48fs)

HGVS:

NC_000023.11:g.103785719_103785729del
NG_008863.2:g.14209_14219del
NG_016452.2:g.51556_51566del
NM_000533.5:c.142_152delMANE SELECT
NM_001128834.3:c.142_152del
NM_001305004.1:c.5-28_5-18del
NM_199478.3:c.142_152del
NP_000524.3:p.Glu48fs
NP_001122306.1:p.Glu48fs
NP_955772.1:p.Glu48fs
NC_000023.10:g.103040646_103040656del
NC_000023.10:g.103040648_103040658del

Protein change:

E48fs

Molecular consequence:

NM_000533.5:c.142_152del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001128834.3:c.142_152del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_199478.3:c.142_152del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001305004.1:c.5-28_5-18del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Hereditary spastic paraplegia 2 (SPG2)
Synonyms:: SPASTIC PARAPLEGIA 2, X-LINKED; Spastic paraplegia 2
Identifiers:: MONDO: MONDO:0010733; MedGen: C1839264; Orphanet: 99015; OMIM: 312920

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002969725	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 28, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18470932, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002969725

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 28, 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

PLP1 splicing abnormalities identified in Pelizaeus-Merzbacher disease and SPG2 fibroblasts are associated with different types of mutations.

Bonnet-Dupeyron MN, Combes P, Santander P, Cailloux F, Boespflug-Tanguy O, Vaurs-Barrière C.

Hum Mutat. 2008 Aug;29(8):1028-36. doi: 10.1002/humu.20758.

PubMed [citation]

PMID:: 18470932

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, SCV002969725.2

#	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. This variant has not been reported in the literature in individuals affected with PLP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu48Leufs*8) in the PLP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PLP1 are known to be pathogenic (PMID: 18470932).

#	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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