NM_007194.4(CHEK2):c.234_262del (p.Gln78fs) AND Familial cancer of breast

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 31, 2019
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:: RCV001042203.7

Allele description [Variation Report for NM_007194.4(CHEK2):c.234_262del (p.Gln78fs)]

NM_007194.4(CHEK2):c.234_262del (p.Gln78fs)

Gene:

CHEK2:checkpoint kinase 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

22q12.1

Genomic location:

Preferred name:

NM_007194.4(CHEK2):c.234_262del (p.Gln78fs)

HGVS:

NC_000022.11:g.28734460_28734488del
NG_008150.2:g.12379_12407del
NM_001005735.2:c.234_262del
NM_001257387.2:c.-544_-516del
NM_001349956.2:c.234_262del
NM_007194.4:c.234_262delMANE SELECT
NM_145862.2:c.234_262del
NP_001005735.1:p.Gln78fs
NP_001336885.1:p.Gln78fs
NP_009125.1:p.Gln78fs
NP_665861.1:p.Gln78fs
LRG_302t1:c.234_262del
LRG_302:g.12379_12407del
LRG_302p1:p.Gln78fs
NC_000022.10:g.29130448_29130476del
NG_008150.1:g.12347_12375del
NM_007194.3:c.234_262del

Protein change:

Q78fs

Links:

dbSNP: rs2054316045

NCBI 1000 Genomes Browser:

rs2054316045

Molecular consequence:

NM_001257387.2:c.-544_-516del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001005735.2:c.234_262del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001349956.2:c.234_262del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_007194.4:c.234_262del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_145862.2:c.234_262del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Intracellular Membranes
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Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDR...<br/>Year introduced: 1979

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Macrostomia
Macrostomia
Greatly exaggerated width of the mouth, resulting from failure of union of the maxillary and mandibular processes, with extension of the oral orifice toward the ear. The defec...<br/>Year introduced: 1965

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001205873	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 31, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21876083, 24713400, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001205873

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 31, 2019)

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

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

A risk of breast cancer in women - carriers of constitutional CHEK2 gene mutations, originating from the North - Central Poland.

Bąk A, Janiszewska H, Junkiert-Czarnecka A, Heise M, Pilarska-Deltow M, Laskowski R, Pasińska M, Haus O.

Hered Cancer Clin Pract. 2014 Apr 8;12(1):10. doi: 10.1186/1897-4287-12-10.

PubMed [citation]

PMID:: 24713400
PMCID:: PMC3991918

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001205873.5

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

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). This variant has not been reported in the literature in individuals with CHEK2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln78Hisfs*20) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product.

#	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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