NM_000222.3(KIT):c.1775-2A>G AND Gastrointestinal stromal tumor

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 18, 2018
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:: RCV000792285.6

Allele description [Variation Report for NM_000222.3(KIT):c.1775-2A>G]

NM_000222.3(KIT):c.1775-2A>G

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

4q12

Genomic location:

Preferred name:

NM_000222.3(KIT):c.1775-2A>G

HGVS:

NC_000004.12:g.54727821A>G
NG_007456.1:g.74827A>G
NM_000222.3:c.1775-2A>GMANE SELECT
NM_001093772.2:c.1763-2A>G
NM_001385284.1:c.1778-2A>G
NM_001385285.1:c.1775-2A>G
NM_001385286.1:c.1763-2A>G
NM_001385288.1:c.1766-2A>G
NM_001385290.1:c.1778-2A>G
NM_001385292.1:c.1766-2A>G
LRG_307t1:c.1775-2A>G
LRG_307:g.74827A>G
NC_000004.11:g.55593987A>G
NM_000222.2:c.1775-2A>G

Links:

dbSNP: rs1577995761

NCBI 1000 Genomes Browser:

rs1577995761

Molecular consequence:

NM_000222.3:c.1775-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001093772.2:c.1763-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001385284.1:c.1778-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001385285.1:c.1775-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001385286.1:c.1763-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001385288.1:c.1766-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001385290.1:c.1778-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001385292.1:c.1766-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000931571	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 18, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16199547, 15194144, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000931571

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 18, 2018)

germline

clinical testing

PubMed (3)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000931571.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 11 of the KIT gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in KIT are known to be pathogenic (PMID: 15194144). This variant has not been reported in the literature in individuals with KIT-related disease.

#	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: Sep 29, 2024

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