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NM_007194.4(CHEK2):c.1096-2A>G AND Familial cancer of breast

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 1, 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:
RCV001989399.5

Allele description [Variation Report for NM_007194.4(CHEK2):c.1096-2A>G]

NM_007194.4(CHEK2):c.1096-2A>G

Gene:
CHEK2:checkpoint kinase 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
22q12.1
Genomic location:
Preferred name:
NM_007194.4(CHEK2):c.1096-2A>G
HGVS:
  • NC_000022.11:g.28695875T>C
  • NG_008150.2:g.50992A>G
  • NM_001005735.2:c.1225-2A>G
  • NM_001257387.2:c.433-2A>G
  • NM_001349956.2:c.895-2A>G
  • NM_007194.3:c.1096-2A>G
  • NM_007194.4:c.1096-2A>GMANE SELECT
  • NM_145862.2:c.1009-2A>G
  • LRG_302t1:c.1096-2A>G
  • LRG_302:g.50992A>G
  • NC_000022.10:g.29091863T>C
Links:
dbSNP: rs2145807398
NCBI 1000 Genomes Browser:
rs2145807398
Molecular consequence:
  • NM_001005735.2:c.1225-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001257387.2:c.433-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001349956.2:c.895-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_007194.4:c.1096-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_145862.2:c.1009-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Familial cancer of breast
Synonyms:
Breast cancer, familial; Hereditary breast cancer
Identifiers:
MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002282610Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jun 1, 2023) 		germlineclinical testing

PubMed (4)
[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

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

Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer.

Cybulski C, Wokołorczyk D, Jakubowska A, Huzarski T, Byrski T, Gronwald J, Masojć B, Deebniak T, Górski B, Blecharz P, Narod SA, Lubiński J.

J Clin Oncol. 2011 Oct 1;29(28):3747-52. doi: 10.1200/JCO.2010.34.0778. Epub 2011 Aug 29.

PubMed [citation]
PMID:
21876083
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002282610.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1494515). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 10 of the CHEK2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400).

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

Last Updated: Sep 29, 2024