NM_000533.5(PLP1):c.105T>A (p.Cys35Ter) AND Pelizaeus-Merzbacher disease

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 16, 2021
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:: RCV004595759.1

Allele description [Variation Report for NM_000533.5(PLP1):c.105T>A (p.Cys35Ter)]

NM_000533.5(PLP1):c.105T>A (p.Cys35Ter)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

Xq22.2

Genomic location:

Preferred name:

NM_000533.5(PLP1):c.105T>A (p.Cys35Ter)

HGVS:

NC_000023.11:g.103785682T>A
NG_008863.2:g.14172T>A
NG_016452.2:g.51601A>T
NM_000533.5:c.105T>AMANE SELECT
NM_001128834.3:c.105T>A
NM_001305004.1:c.5-65T>A
NM_199478.3:c.105T>A
NP_000524.3:p.Cys35Ter
NP_001122306.1:p.Cys35Ter
NP_955772.1:p.Cys35Ter
NC_000023.10:g.103040611T>A

Protein change:

C35*

Molecular consequence:

NM_001305004.1:c.5-65T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000533.5:c.105T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001128834.3:c.105T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_199478.3:c.105T>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV005088434	Molecular Diagnostics Lab, Nemours Children's Health, Delaware	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 16, 2021)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15712223, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005088434

Molecular Diagnostics Lab, Nemours Children's Health, Delaware

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 16, 2021)

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

Seventeen novel PLP1 mutations in patients with Pelizaeus-Merzbacher disease.

Hübner CA, Orth U, Senning A, Steglich C, Kohlschütter A, Korinthenberg R, Gal A.

Hum Mutat. 2005 Mar;25(3):321-2.

PubMed [citation]

PMID:: 15712223

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, SCV005088434.1

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

Description

This nonsense variant (c.105T>A, p.Cys35*) has not been observed in population databases (gnomAD). It has been described in the literature (PMID 1572223). 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	blood	not provided	(GTR000028364.3)	1	not provided	not provided	not provided

Last Updated: Jul 29, 2024

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