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NM_000533.5(PLP1):c.282del (p.Gly95fs) AND Pelizaeus-Merzbacher disease

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 31, 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:
RCV004595764.1

Allele description [Variation Report for NM_000533.5(PLP1):c.282del (p.Gly95fs)]

NM_000533.5(PLP1):c.282del (p.Gly95fs)

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.282del (p.Gly95fs)
HGVS:
  • NC_000023.11:g.103786555del
  • NG_008863.2:g.15045del
  • NG_016452.2:g.50729del
  • NM_000533.5:c.282delMANE SELECT
  • NM_001128834.3:c.282del
  • NM_001305004.1:c.117del
  • NM_199478.3:c.282del
  • NP_000524.3:p.Gly95fs
  • NP_001122306.1:p.Gly95fs
  • NP_001291933.1:p.Gly40fs
  • NP_955772.1:p.Gly95fs
  • NC_000023.10:g.103041484del
  • NM_000533.5:c.282delCMANE SELECT
Protein change:
G40fs
Molecular consequence:
  • NM_000533.5:c.282del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001128834.3:c.282del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001305004.1:c.117del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_199478.3:c.282del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
4

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005088440Molecular Diagnostics Lab, Nemours Children's Health, Delaware
criteria provided, single submitter

(ACMG Guidelines, 2015)		pathogenic
(Mar 31, 2021) 		maternal, unknownclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedmaternalyes2not providednot provided2not providedclinical testing
not providedunknownno2not providednot provided2not providedclinical testing

Citations

PubMed

Neuroradiologic correlates of clinical disability and progression in the X-linked leukodystrophy Pelizaeus-Merzbacher disease.

Laukka JJ, Stanley JA, Garbern JY, Trepanier A, Hobson G, Lafleur T, Gow A, Kamholz J.

J Neurol Sci. 2013 Dec 15;335(1-2):75-81. doi: 10.1016/j.jns.2013.08.030. Epub 2013 Aug 30.

PubMed [citation]
PMID:
24139698
PMCID:
PMC3969727

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, SCV005088440.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing
(GTR000028364.3)		 PubMed (2)
2not provided1not providednot providedclinical testing
(GTR000028364.3)		 PubMed (2)
3not provided1not providednot providedclinical testing
(GTR000028364.3)		 PubMed (2)
4not provided1not providednot providedclinical testing
(GTR000028364.3)		 PubMed (2)

Description

This variant (c.282delC, p.Gly95Alafs*19) results in a frameshift to a premature termination. It has not been observed in population databases (gnomAD), but it has been described in the literature (PMID:24139698). This change has been found in 2 affected males within a family who are related through maternal lines, and both mothers are heterozygous carriers. No functional studies have been published.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1maternalyes1bloodnot provided
(GTR000028364.3)		1not providednot providednot provided
2unknownno1bloodnot provided
(GTR000028364.3)		1not providednot providednot provided
3maternalyes1bloodnot provided
(GTR000028364.3)		1not providednot providednot provided
4unknownno1bloodnot provided
(GTR000028364.3)		1not providednot providednot provided

Last Updated: Jul 29, 2024