VCV000014678.4 - ClinVar

NC_000002.12:g.112960554_113135775del

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

Identifiers

NC_000002.12:g.112960554_113135775del

Variation ID: 14678 Accession: VCV000014678.4

Type and length

Deletion, -

Location

Cytogenetic: 2q14.2 -

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 3, 2013	Aug 5, 2023	Jun 4, 2009

HGVS

Nucleotide	Protein	Molecular consequence
NC_000002.12:g.112960554_113135775del
NC_000002.10:g.113434602_113609823del

Protein change

Other names

175-KB 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: 147679.0005

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.
IL1RN		-	-	GRCh38 GRCh37	224	247

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.
Sterile multifocal osteomyelitis with periostitis and pustulosis	Pathogenic (1)	no assertion criteria provided	Jun 4, 2009	RCV000015792.29

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 (Jun 04, 2009)	no assertion criteria provided Method: literature only	CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS 2, WITH PERIOSTITIS AND PUSTULOSIS Affected status: not provided Allele origin: germline	OMIM Accession: SCV000036059.5 First in ClinVar: Apr 04, 2013 Last updated: Aug 05, 2023	Publications: PubMed (2) PubMed: 19494218‚ 19494219 Comment on evidence: In a child from a family originating from Puerto Rico who had neonatal onset of chronic recurrent multifocal osteomyelitis-2 with periostitis and pustulosis (CRMO2; 612852), … (more) In a child from a family originating from Puerto Rico who had neonatal onset of chronic recurrent multifocal osteomyelitis-2 with periostitis and pustulosis (CRMO2; 612852), Aksentijevich et al. (2009) identified homozygosity for a 175-kb deletion that encompassed 6 IL1-related genes: IL1RN, IL1F9 (605542), IL1F6 (605509), IL1F8 (605508), IL1F5 (605507), and IL1F10 (615296). Quantitative PCR of whole blood from the patient revealed complete absence of IL1RN mRNA. His unaffected parents and sister were heterozygous for the deletion, which was also found in 3 unrelated carriers from a panel of 119 geographically matched controls, suggesting a founder effect. The patient responded rapidly to treatment with human recombinant IL1RN anakinra. In an 18-month-old male infant with neonatal onset of pustular rash, osteopenia, lytic bone lesions, respiratory insufficiency, and thrombosis, Reddy et al. (2009) identified homozygosity for the 175-kb deletion. The unaffected parents were heterozygous for the deletion. Anakinra treatment completely resolved the symptoms and lesions. (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
An autoinflammatory disease due to homozygous deletion of the IL1RN locus.	Reddy S	The New England journal of medicine	2009	PMID: 19494219
An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist.	Aksentijevich I	The New England journal of medicine	2009	PMID: 19494218

Text-mined citations for this variant ...

Record last updated Aug 06, 2023

ClinVar Genomic variation as it relates to human health

NC_000002.12:g.112960554_113135775del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...