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NM_000222.3(KIT):c.2459A>G (p.Asp820Gly) AND Gastrointestinal stromal tumor

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 12, 2022
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:
RCV001303922.6

Allele description [Variation Report for NM_000222.3(KIT):c.2459A>G (p.Asp820Gly)]

NM_000222.3(KIT):c.2459A>G (p.Asp820Gly)

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.2459A>G (p.Asp820Gly)
HGVS:
  • NC_000004.12:g.54733167A>G
  • NG_007456.1:g.80173A>G
  • NM_000222.3:c.2459A>GMANE SELECT
  • NM_001093772.2:c.2447A>G
  • NM_001385284.1:c.2462A>G
  • NM_001385285.1:c.2456A>G
  • NM_001385286.1:c.2444A>G
  • NM_001385288.1:c.2450A>G
  • NM_001385290.1:c.2459A>G
  • NM_001385292.1:c.2447A>G
  • NP_000213.1:p.Asp820Gly
  • NP_001087241.1:p.Asp816Gly
  • NP_001372213.1:p.Asp821Gly
  • NP_001372214.1:p.Asp819Gly
  • NP_001372215.1:p.Asp815Gly
  • NP_001372217.1:p.Asp817Gly
  • NP_001372219.1:p.Asp820Gly
  • NP_001372221.1:p.Asp816Gly
  • LRG_307:g.80173A>G
  • NC_000004.11:g.55599333A>G
  • P10721:p.Asp820Gly
Protein change:
D815G; ASP820GLY
Links:
UniProtKB: P10721#VAR_033135; OMIM: 164920.0010; dbSNP: rs121913682
NCBI 1000 Genomes Browser:
rs121913682
Molecular consequence:
  • NM_000222.3:c.2459A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001093772.2:c.2447A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385284.1:c.2462A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385285.1:c.2456A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385286.1:c.2444A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385288.1:c.2450A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385290.1:c.2459A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001385292.1:c.2447A>G - missense variant - [Sequence Ontology: SO:0001583]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001493189Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 12, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Familial gastrointestinal stromal tumors associated with dysphagia and novel type germline mutation of KIT gene.

Hirota S, Nishida T, Isozaki K, Taniguchi M, Nishikawa K, Ohashi A, Takabayashi A, Obayashi T, Okuno T, Kinoshita K, Chen H, Shinomura Y, Kitamura Y.

Gastroenterology. 2002 May;122(5):1493-9.

PubMed [citation]
PMID:
11984533

Hereditary gastrointestinal stromal tumors sharing the KIT Exon 17 germline mutation p.Asp820Tyr develop through different cytogenetic progression pathways.

Veiga I, Silva M, Vieira J, Pinto C, Pinheiro M, Torres L, Soares M, Santos L, Duarte H, Bastos AL, Coutinho C, Dinis J, Lopes C, Teixeira MR.

Genes Chromosomes Cancer. 2010 Feb;49(2):91-8. doi: 10.1002/gcc.20720.

PubMed [citation]
PMID:
19847891
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001493189.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Asp820 amino acid residue in KIT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11984533, 19847891). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 13853). This missense change has been observed in individual(s) with gastrointestinal stromal tumors (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 820 of the KIT protein (p.Asp820Gly).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024