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NM_007194.4(CHEK2):c.1100del (p.Thr367fs) AND Ovarian neoplasm

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 28, 2023
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV003445511.1

Allele description [Variation Report for NM_007194.4(CHEK2):c.1100del (p.Thr367fs)]

NM_007194.4(CHEK2):c.1100del (p.Thr367fs)

Gene:
CHEK2:checkpoint kinase 2 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
22q12.1
Genomic location:
Preferred name:
NM_007194.4(CHEK2):c.1100del (p.Thr367fs)
Other names:
NP_009125.1:p.Thr367MetfsTer15
HGVS:
  • NC_000022.11:g.28695869del
  • NG_008150.2:g.50998del
  • NM_001005735.2:c.1229del
  • NM_001257387.2:c.437del
  • NM_001349956.2:c.899del
  • NM_007194.4:c.1100delMANE SELECT
  • NM_145862.2:c.1013del
  • NP_001005735.1:p.Thr410fs
  • NP_001244316.1:p.Thr146fs
  • NP_001336885.1:p.Thr300fs
  • NP_009125.1:p.Thr367fs
  • NP_665861.1:p.Thr338fs
  • LRG_302t1:c.1100del
  • LRG_302:g.50998del
  • LRG_302p1:p.Thr367fs
  • NC_000022.10:g.29091857del
  • NC_000022.10:g.29091857delG
  • NG_008150.1:g.50966del
  • NM_001005735.1:c.1229del
  • NM_001005735.1:c.1229delC
  • NM_001005735.2:c.1229delC
  • NM_007194.3:c.1100delC
  • NM_007194.4:c.1100delCMANE SELECT
  • c.1100delC
  • p.T367MFS*15
  • p.T367MfsX15
  • p.Thr367Metfs*15
  • p.Thr367MetfsX15
  • p.Thr367fs
  • p.Thr410fs
Protein change:
T146fs
Links:
OMIM: 604373.0001; dbSNP: rs555607708
NCBI 1000 Genomes Browser:
rs555607708
Molecular consequence:
  • NM_001005735.2:c.1229del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001257387.2:c.437del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001349956.2:c.899del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_007194.4:c.1100del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_145862.2:c.1013del - frameshift variant - [Sequence Ontology: SO:0001589]
Functional consequence:
Uncertain function
Observations:
1

Condition(s)

Name:
Ovarian neoplasm
Synonyms:
Neoplasm of ovary; Ovarian tumor; Ovarian Neoplasms
Identifiers:
MONDO: MONDO:0021068; MeSH: D010051; MedGen: C0919267; Human Phenotype Ontology: HP:0100615

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004174182Diagnostics Centre, Carl Von Ossietzky University Oldenburg
no assertion criteria provided
Pathogenic
(Jul 28, 2023) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

The CHEK2*1100delC allelic variant and risk of breast cancer: screening results from the Breast Cancer Family Registry.

Bernstein JL, Teraoka SN, John EM, Andrulis IL, Knight JA, Lapinski R, Olson ER, Wolitzer AL, Seminara D, Whittemore AS, Concannon P.

Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):348-52.

PubMed [citation]
PMID:
16492927

CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer.

Weischer M, Nordestgaard BG, Pharoah P, Bolla MK, Nevanlinna H, Van't Veer LJ, Garcia-Closas M, Hopper JL, Hall P, Andrulis IL, Devilee P, Fasching PA, Anton-Culver H, Lambrechts D, Hooning M, Cox A, Giles GG, Burwinkel B, Lindblom A, Couch FJ, Mannermaa A, Grenaker Alnæs G, et al.

J Clin Oncol. 2012 Dec 10;30(35):4308-16. doi: 10.1200/JCO.2012.42.7336. Epub 2012 Oct 29.

PubMed [citation]
PMID:
23109706
PMCID:
PMC3515767
See all PubMed Citations (6)

Details of each submission

From Diagnostics Centre, Carl Von Ossietzky University Oldenburg, SCV004174182.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (6)

Description

The variant CHEK2:c.1100delC, p.(Thr367fs), which is located in the coding exon 11 of the CHEK2 gene, results from a deletion of a nucleotide at position 1100. The variant causes a frameshift that results on the replace of threonine residue at protein position 367 by methionine and a premature stop codon follows after further 15 amino acids. The premature stop codon is predicted to cause protein truncation/absent and nonsense mediated decay in a gene where loss-of-function is a mechanism of disease. Multiple studies has shown that the variant is statistically significant associated to increased risk of breast and other type of cancer, including ovarian cancer (PMID: 16492927; 23109706; 21956126; 16880452; 28727877; 37055167). In one study, tumours were also detected statistically significantly more frequently in mice with the CHEK2 c.1100delC variant as compared to wild-type controls (PMID: 19805189). This variant is a known founder variant in the overall population and occurs with an allele frequency of < 1 % in gnomAD. The variant is classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Nov 3, 2024