VCV000915458.2 - ClinVar

NM_005573.4(LMNB1):c.939+2362_1491+560del

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.

(2)

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.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_005573.4(LMNB1):c.939+2362_1491+560del

Variation ID: 915458 Accession: VCV000915458.2

Type and length

Deletion, 9,186 bp

Location

Cytogenetic: 5q23.2 5: 126814259-126823444 (GRCh38) [ NCBI UCSC ] 5: 126149951-126159136 (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	Aug 23, 2020	Feb 28, 2021	Feb 19, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_005573.4:c.939+2362_1491+560del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice acceptor splice donor
NM_001198557.2:c.309+2362_861+560del		splice acceptor splice donor
NC_000005.10:g.126814260_126823445del
NC_000005.9:g.126149952_126159137del
NG_008360.2:g.42120_51305del

... more HGVS ... less HGVS

Protein change

Other names

5q23.2(126,149,952-126,159,137)x1mat
EX6-8 DEL

Canonical SPDI

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

OMIM: 150340.0003 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.
LMNB1		No evidence available	Sufficient evidence for dosage pathogenicity	GRCh38 GRCh37	247	286

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.
Syndrome with microcephaly as major feature	Pathogenic (1)	no assertion criteria provided	Feb 20, 2020	RCV001254644.1
Microcephaly 26, primary, autosomal dominant	Pathogenic (1)	no assertion criteria provided	Feb 19, 2021	RCV002287475.1

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.
Pathogenic (Feb 20, 2020)	no assertion criteria provided Method: clinical testing	Syndrome with microcephaly as major feature (Autosomal dominant inheritance) Affected status: yes Allele origin: maternal	Center for Human Genetics, University of Leuven Accession: SCV001296963.1 First in ClinVar: Aug 23, 2020 Last updated: Aug 23, 2020	Comment: We performed segregation analysis, Western blot, and several functional in vitro studies that support a clear pathogenic effect
Pathogenic (Feb 19, 2021)	no assertion criteria provided Method: literature only	MICROCEPHALY 26, PRIMARY, AUTOSOMAL DOMINANT Affected status: not provided Allele origin: germline	OMIM Accession: SCV001481150.1 First in ClinVar: Feb 28, 2021 Last updated: Feb 28, 2021	Publications: PubMed (1) PubMed: 32910914 Comment on evidence: In a 9-year-old Belgian girl (P2) with autosomal dominant primary microcephaly-26 (MCPH26; 619179), Cristofoli et al. (2020) identified a heterozygous in-frame deletion in the LMNB1 … (more) In a 9-year-old Belgian girl (P2) with autosomal dominant primary microcephaly-26 (MCPH26; 619179), Cristofoli et al. (2020) identified a heterozygous in-frame deletion in the LMNB1 gene, causing the deletion of exons 6-8 (Ser314_Thr497del). The deletion, which was found by microarray analysis, was inherited from the similarly affected mother in whom it occurred de novo. The deletion was predicted to result in a shortened protein lacking the nuclear localization signal. The authors postulated that the mutation results in insufficient protein abundance in the nucleus to form a stable laminar network and acts in a dominant-negative manner. However, functional studies of the variant and studies of patient cells were not performed. These patients had a milder phenotype than the others: the proband had a head circumference (HC) of -3.6 SD, whereas her mother had a HC of -2.5 SD and had learning difficulties. (less)

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
De Novo Variants in LMNB1 Cause Pronounced Syndromic Microcephaly and Disruption of Nuclear Envelope Integrity.	Cristofoli F	American journal of human genetics	2020	PMID: 32910914

Text-mined citations for this variant ...

Record last updated Dec 25, 2023

ClinVar Genomic variation as it relates to human health

NM_005573.4(LMNB1):c.939+2362_1491+560del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...