VCV000242987.1 - ClinVar

NM_033116.4(NEK9):c.[1715G>T;1731+1G>T]

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.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This haplotype includes the following variants

NM_033116.4(NEK9):c.[1715G>T;1731+1G>T]

Other names: NEK9, GLY572VAL AND IVS14, G-T, +1
Functional consequence: -
Links: ClinGen: CA645372566; OMIM: 609798.0003

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.
NEK9		-	-	GRCh38 GRCh37	135	152

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.
Nevus comedonicus syndrome	Pathogenic (1)	no assertion criteria provided	Jul 11, 2016	RCV000234965.2

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.
Pathogenic (Jul 11, 2016)	no assertion criteria provided Method: literature only	NEVUS COMEDONICUS, SOMATIC Affected status: not provided Allele origin: somatic	OMIM Accession: SCV000292296.1 First in ClinVar: Jul 15, 2016 Last updated: Jul 15, 2016	Publications: PubMed (1) PubMed: 27153399 Comment on evidence: In lesional tissue from a 43-year-old woman with nevus comedonicus (NC; 617025), Levinsohn et al. (2016) identified heterozygosity for 2 somatic NEK9 mutations, located in … (more) In lesional tissue from a 43-year-old woman with nevus comedonicus (NC; 617025), Levinsohn et al. (2016) identified heterozygosity for 2 somatic NEK9 mutations, located in cis: a c.1715G-T transversion (c.1715G-T, NM_033116.4) in exon 14, resulting in a gly571-to-val substitution (G572V) predicted to generate a cryptic splice donor site, and a c.1731+1G-T transversion (c.1731+1G-T, NM_033116.4) in intron 14, which abolishes a native splice donor site. Both mutations occurred at highly conserved residues within the regulator of chromosome condensation-like (RCC1) domain of NEK9, and neither was found in DNA from the patient's blood or in the ExAC, Exome Variant Server, or 1000 Genomes Project databases. Analysis of PCR products from transfected PLC cells demonstrated the in-frame loss of 18 nucleotides in the encoded mRNA, corresponding to the deletion of 6 highly conserved amino acids (Gly572_Glu577del). Functional analysis in transiently transfected HEK293 cells demonstrated that the Gly572_Glu577del mutant causes a significant increase in phosphorylation of Thr210, which lies within the activation loop of NEK9; phosphorylation at Thr210 is required for kinase activity. Levinsohn et al. (2016) concluded that this represents a gain-of-function effect. (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
Somatic Mutations in NEK9 Cause Nevus Comedonicus.	Levinsohn JL	American journal of human genetics	2016	PMID: 27153399

Text-mined citations for this variant ...

Record last updated Jan 26, 2024

ClinVar Genomic variation as it relates to human health

NM_033116.4(NEK9):c.[1715G>T;1731+1G>T]

Variant Details

NM_033116.4(NEK9):c.[1715G>T;1731+1G>T]

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...