VCV000004277.4 - ClinVar

NM_025194.3(ITPKC):c.1155+9G>C

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.

Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(1)

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_025194.3(ITPKC):c.1155+9G>C

Variation ID: 4277 Accession: VCV000004277.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19q13.2 19: 40718299 (GRCh38) [ NCBI UCSC ] 19: 41224204 (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	Apr 4, 2013	Oct 8, 2024	Nov 15, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NM_025194.3:c.1155+9G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NC_000019.10:g.40718299G>C
NC_000019.9:g.41224204G>C
NG_012970.1:g.6197G>C
NG_027800.1:g.3587C>G

... more HGVS ... less HGVS

Protein change

Other names

IVS1, G/C

Canonical SPDI

NC_000019.10:40718298:G:C

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.

0.08586 (C)

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

1000 Genomes Project 30x 0.08167

1000 Genomes Project 0.08586

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.08848

Trans-Omics for Precision Medicine (TOPMed) 0.09770

The Genome Aggregation Database (gnomAD) 0.10089

Exome Aggregation Consortium (ExAC) 0.12437

Links

ClinGen: CA9450777 OMIM: 606476.0001 dbSNP: rs28493229 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.
ITPKC		-	-	GRCh38 GRCh37	66	81

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.
ITPKC-related disorder	Benign (1)	no assertion criteria provided	Nov 15, 2019	RCV003974794.2
Reclassified - variant of unknown significance	Uncertain significance (1)	no assertion criteria provided	Mar 15, 2010	RCV004558236.1

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.
Benign (Nov 15, 2019)	no assertion criteria provided Method: clinical testing	ITPKC-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004798364.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Uncertain significance (Mar 15, 2010)	no assertion criteria provided Method: literature only	RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE Affected status: not provided Allele origin: germline	OMIM Accession: SCV000024672.2 First in ClinVar: Apr 04, 2013 Last updated: Jun 09, 2024	Publications: PubMed (2) PubMed: 18084290‚ 20045869 Hamosh, A. Personal Communication. (more...) Hamosh, A. Personal Communication. 2020. Baltimore, Md. Comment on evidence: This variant, formerly titled KAWASAKI DISEASE, SUSCEPTIBILITY TO, has been reclassified because its contribution to the disorder not been confirmed. Onouchi et al. (2008) found … (more) This variant, formerly titled KAWASAKI DISEASE, SUSCEPTIBILITY TO, has been reclassified because its contribution to the disorder not been confirmed. Onouchi et al. (2008) found a significant association between susceptibility to Kawasaki disease (611775) and a functional SNP, which the authors designated itpkc_3 (rs28493229), in the ITPKC gene. It was associated also with increase in coronary artery lesions in both Japanese and U.S. children. Among 78 affected Japanese sib pairs, 40 pairs shared more than one allele near itpkc_3; in this subset, the itpkc_3 allele was overrepresented compared to controls (OR = 2.46, 95% CI 1.63-3.73). The C allele of rs28493229 was associated with the increased risk. In an association study involving 385 unrelated Taiwanese children with Kawasaki disease, 140 with coronary artery lesions, and 1,158 ethnically matched healthy controls, Chi et al. (2010) did not find a statistically significant association between the ITPKC gene SNP rs28493229 and Kawasaki disease or coronary artery lesions in Taiwanese children. Hamosh (2020) found that this G-C variant was present in 23,577 of 198,428 alleles and in 1,596 homozygotes in the gnomAD database, with an overall frequency of 0.1188 (May 6, 2020). (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
ITPKC gene SNP rs28493229 and Kawasaki disease in Taiwanese children.	Chi H	Human molecular genetics	2010	PMID: 20045869
ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms.	Onouchi Y	Nature genetics	2008	PMID: 18084290
Hamosh, A. Personal Communication. 2020. Baltimore, Md.	-	-	-	-

Text-mined citations for rs28493229 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 30, 2024

ClinVar Genomic variation as it relates to human health

NM_025194.3(ITPKC):c.1155+9G>C

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs28493229 ...