NM_000222.3(KIT):c.1990+1del AND Gastrointestinal stromal tumor

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 29, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001965129.4

Allele description [Variation Report for NM_000222.3(KIT):c.1990+1del]

NM_000222.3(KIT):c.1990+1del

Gene:

KIT:KIT proto-oncogene, receptor tyrosine kinase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

4q12

Genomic location:

Preferred name:

NM_000222.3(KIT):c.1990+1del

HGVS:

NC_000004.12:g.54728122del
NG_007456.1:g.75128del
NM_000222.3:c.1990+1delMANE SELECT
NM_001093772.2:c.1978+1del
NM_001385284.1:c.1993+1del
NM_001385285.1:c.1990+1del
NM_001385286.1:c.1978+1del
NM_001385288.1:c.1981+1del
NM_001385290.1:c.1993+1del
NM_001385292.1:c.1981+1del
LRG_307:g.75128del
NC_000004.11:g.55594287del
NC_000004.11:g.55594288del

Links:

dbSNP: rs2109782285

NCBI 1000 Genomes Browser:

rs2109782285

Molecular consequence:

NM_000222.3:c.1990+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001093772.2:c.1978+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001385284.1:c.1993+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001385285.1:c.1990+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001385286.1:c.1978+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001385288.1:c.1981+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001385290.1:c.1993+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001385292.1:c.1981+1del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Gastrointestinal stromal tumor
Synonyms:: Gastrointestinal Stromal Sarcoma; Gastrointestinal stromal tumor, somatic; Gastrointestinal stroma tumor
Identifiers:: MONDO: MONDO:0011719; MeSH: D046152; MedGen: C0238198; Orphanet: 44890; OMIM: 606764; Human Phenotype Ontology: HP:0100723

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activin receptor type-2A isoform 1 precursor [Homo sapiens]
activin receptor type-2A isoform 1 precursor [Homo sapiens]
gi|4501897|ref|NP_001607.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002210025	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 29, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15194144, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002210025

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 29, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

New KIT mutations in patients with piebaldism.

Murakami T, Fukai K, Oiso N, Hosomi N, Kato A, Garganta C, Barnicoat A, Poppelaars F, Aquaron R, Paller AS, Ishii M.

J Dermatol Sci. 2004 Jun;35(1):29-33.

PubMed [citation]

PMID:: 15194144

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002210025.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Thr666Profs*14) in the KIT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KIT are known to be pathogenic (PMID: 15194144). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KIT-related conditions. This variant is also known as c.1990+1del. ClinVar contains an entry for this variant (Variation ID: 1438243). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 15, 2024

ClinVar

Relating variation to medicine