NM_000533.5(PLP1):c.554_564del (p.Gln185fs) AND Pelizaeus-Merzbacher disease

Germline classification:: Likely pathogenic (1 submission)
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:: RCV004588588.2

Allele description [Variation Report for NM_000533.5(PLP1):c.554_564del (p.Gln185fs)]

NM_000533.5(PLP1):c.554_564del (p.Gln185fs)

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.554_564del (p.Gln185fs)

HGVS:

NC_000023.11:g.103787898_103787908del
NG_008863.2:g.16388_16398del
NG_016452.2:g.49379_49389del
NM_000533.5:c.554_564delMANE SELECT
NM_001128834.3:c.554_564del
NM_001305004.1:c.389_399del
NM_199478.3:c.449_459del
NP_000524.3:p.Gln185fs
NP_001122306.1:p.Gln185fs
NP_001291933.1:p.Gln130fs
NP_955772.1:p.Gln150fs
NC_000023.10:g.103042827_103042837del

Protein change:

Q130fs

Molecular consequence:

NM_000533.5:c.554_564del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001128834.3:c.554_564del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001305004.1:c.389_399del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_199478.3:c.449_459del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Pelizaeus-Merzbacher disease
Synonyms:: LEUKODYSTROPHY, HYPOMYELINATING, 1; Pelizaeus Merzbacher brain sclerosis; Sudanophilic leukodystrophy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010714; MedGen: C0205711; Orphanet: 702; OMIM: 312080; Human Phenotype Ontology: HP:0003269

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005077963	Molecular Diagnostics Lab, Nemours Children's Health, Delaware	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21679407, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005077963

Molecular Diagnostics Lab, Nemours Children's Health, Delaware

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

unknown

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	unknown	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Molecular genetic analysis of the PLP1 gene in 38 families with PLP1-related disorders: identification and functional characterization of 11 novel PLP1 mutations.

Grossi S, Regis S, Biancheri R, Mort M, Lualdi S, Bertini E, Uziel G, Boespflug-Tanguy O, Simonati A, Corsolini F, Demir E, Marchiani V, Percesepe A, Stanzial F, Rossi A, Vaurs-Barrière C, Cooper DN, Filocamo M.

Orphanet J Rare Dis. 2011 Jun 16;6:40. doi: 10.1186/1750-1172-6-40.

PubMed [citation]

PMID:: 21679407
PMCID:: PMC3125326

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Molecular Diagnostics Lab, Nemours Children's Health, Delaware, SCV005077963.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing (GTR000028364.3)	PubMed (2)

Description

This variant (c.554_564del, p.Gln185Leufs*15) predicts a frameshift and a premature termination. It has not been observed in population databases (gnomAD). The change has been described in the literature (PMID 21679497) but no functional studies have been published.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	1	not provided	not provided	(GTR000028364.3)	1	not provided	not provided	not provided

Last Updated: Aug 18, 2024

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