VCV003252100.2 - ClinVar

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

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

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

Variation ID: 3252100 Accession: VCV003252100.2

Type and length

Deletion, 11 bp

Location

Cytogenetic: Xq22.2 X: 103787894-103787904 (GRCh38) [ NCBI UCSC ] X: 103042823-103042833 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 23, 2024	Aug 11, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000533.5:c.554_564del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000524.3:p.Gln185fs	frameshift
NM_001128834.3:c.554_564del	NP_001122306.1:p.Gln185fs	frameshift
NM_001305004.1:c.389_399del	NP_001291933.1:p.Gln130fs	frameshift
NM_199478.3:c.449_459del	NP_955772.1:p.Gln150fs	frameshift
NC_000023.11:g.103787898_103787908del
NC_000023.10:g.103042827_103042837del
NG_008863.2:g.16388_16398del
NG_016452.2:g.49379_49389del

... more HGVS ... less HGVS

Protein change

Q130fs, Q150fs, Q185fs

Other names

Canonical SPDI

NC_000023.11:103787893:TGCCAGTCTATTGCC:TGCC

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
PLP1		Sufficient evidence for dosage pathogenicity	Sufficient evidence for dosage pathogenicity	GRCh38 GRCh37	17	617
RAB9B		-	-	GRCh38 GRCh37	3	602

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Pelizaeus-Merzbacher disease	Likely pathogenic (1)	criteria provided, single submitter	-	RCV004588588.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Pelizaeus-Merzbacher disease Affected status: yes Allele origin: unknown	Molecular Diagnostics Lab, Nemours Children's Health, Delaware Accession: SCV005077963.2 First in ClinVar: Jul 23, 2024 Last updated: Aug 11, 2024	Publications: PubMed (1) PubMed: 21679407 Comment: This variant (c.554_564del, p.Gln185Leufs15) predicts a frameshift and a premature termination. It has not been observed in population databases (gnomAD). The change has been described … (more) This variant (c.554_564del, p.Gln185Leufs15) 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. (less) Clinical Features: Spastic tetraplegia (present) Zygosity: Hemizygote

Comment:

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.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
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	Orphanet journal of rare diseases	2011	PMID: 21679407

Text-mined citations for this variant ...

Record last updated Aug 18, 2024

ClinVar Genomic variation as it relates to human health

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

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...