VCV000222957.2 - ClinVar

NM_000222.3(KIT):c.1669_1674del (p.Trp557_Lys558del)

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

Oncogenicity

The aggregate oncogenicity classification for this variant for one or more tumor types, using the ClinGen/CGC/VICC terminology. 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 oncogenicity 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 oncogenic

no assertion criteria provided

Variant Details

Identifiers

NM_000222.3(KIT):c.1669_1674del (p.Trp557_Lys558del)

Variation ID: 222957 Accession: VCV000222957.2

Type and length

Deletion, 6 bp

Location

Cytogenetic: 4q12 4: 54727435-54727440 (GRCh38) [ NCBI UCSC ] 4: 55593601-55593606 (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	Mar 1, 2016	Mar 1, 2016	Feb 25, 2016
Somatic - Oncogenicity	Jun 23, 2024	Jun 23, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000222.3:c.1669_1674del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000213.1:p.Trp557_Lys558del	inframe deletion
NM_001093772.2:c.1657_1662del	NP_001087241.1:p.Trp553_Lys554del	inframe deletion
NM_001385284.1:c.1672_1677del	NP_001372213.1:p.Trp558_Lys559del	inframe deletion
NM_001385285.1:c.1669_1674del	NP_001372214.1:p.Trp557_Lys558del	inframe deletion
NM_001385286.1:c.1657_1662del	NP_001372215.1:p.Trp553_Lys554del	inframe deletion
NM_001385288.1:c.1660_1665del	NP_001372217.1:p.Trp554_Lys555del	inframe deletion
NM_001385290.1:c.1672_1677del	NP_001372219.1:p.Trp558_Lys559del	inframe deletion
NM_001385292.1:c.1660_1665del	NP_001372221.1:p.Trp554_Lys555del	inframe deletion
NC_000004.12:g.54727437_54727442del
NC_000004.11:g.55593603_55593608del
NG_007456.1:g.74443_74448del
LRG_307:g.74443_74448del

... more HGVS ... less HGVS

Protein change

Other names

Trp557_Lys558del

Canonical SPDI

NC_000004.12:54727434:AGTGGAAG:AG

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

ClinGen: CA356974 dbSNP: rs869025568 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.
KIT		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2888	2916

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.
Gastrointestinal stromal tumor	Likely pathogenic (1)	criteria provided, single submitter	Feb 25, 2016	RCV000208566.3

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 (Feb 25, 2016)	criteria provided, single submitter (Submitter's publication) Method: clinical testing	Gastrointestinal stromal tumor Affected status: yes Allele origin: unknown	QMC Molecular Diagnostics, Queen's Medical Center Accession: SCV000264332.1 First in ClinVar: Mar 01, 2016 Last updated: Mar 01, 2016	Publications: PubMed (1) PubMed: 9438854 Comment: Based on OMIM - Hirota et. al research on GIST molecular profiles. Juxtaposition membrane domain deletions have a consequential affect on physiology and developing GIST. … (more) Based on OMIM - Hirota et. al research on GIST molecular profiles. Juxtaposition membrane domain deletions have a consequential affect on physiology and developing GIST. Though not specifically identified in Pubmed ID - 9438854, the active protein region affected here is encompassed by findings from the paper so the significance is likely pathogenic. (less) Indication for testing: malignant gastrointestinal stromal tumor resected Age: 60-69 years Sex: female Geographic origin: Hawaii Method: FFPE biopsy of tumor microdissected and DNA extracted. PCR amplification of c-kit exons 9,11,13, and 17 (Chen, L. et al, 2004). Cycle sequencing performed and subsequently purified. Products run on the ABI 3500.

Comment:

Based on OMIM - Hirota et. al research on GIST molecular profiles. Juxtaposition membrane domain deletions have a consequential affect on physiology and developing GIST. Though not specifically identified in Pubmed ID - 9438854, the active protein region affected here is encompassed by findings from the paper so the significance is likely pathogenic.

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Conditions - Somatic

Tumor type Help The tumor type for this variant-condition (RCV) record in ClinVar.	Clinical impact (# of submissions) Help The aggregate somatic clinical impact for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate somatic clinical impact is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status.	Oncogenicity Help The aggregate oncogenicity classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate oncogenicity classification is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the tumor type.	Variation/condition record Help The most recent date that a submitter evaluated this variant for the tumor type.
Gastrointestinal stromal tumor		Likely oncogenic no assertion criteria provided	-	RCV000208566.3

Submissions - Somatic

Oncogenicity Help The submitted oncogenicity 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)	Tumor type Help The tumor type 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 somatic clinical impact, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.

Likely oncogenic

(-)

Method: research

Gastrointestinal stromal tumor

Affected status: unknown

Allele origin: somatic

National Institute of Cancer Research, National Health Research Institutes

Accession: SCV005061474.1
First In ClinVar: Jun 23, 2024
Last updated: Jun 23, 2024

Comment:

clinical data

Number of individuals with the variant: 15

Family history: no

Tissue: GIST tumor

Comment:

Citations for somatic classification of this variant

There are no citations for somatic classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs869025568 ...

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 Sep 17, 2024

ClinVar Genomic variation as it relates to human health

NM_000222.3(KIT):c.1669_1674del (p.Trp557_Lys558del)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Conditions - Somatic

Submissions - Somatic

Citations for somatic classification of this variant

Text-mined citations for rs869025568 ...