NM_007194.4(CHEK2):c.129del (p.Ser44fs) AND Familial cancer of breast

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 8, 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:: RCV002861745.3

Allele description [Variation Report for NM_007194.4(CHEK2):c.129del (p.Ser44fs)]

NM_007194.4(CHEK2):c.129del (p.Ser44fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

22q12.1

Genomic location:

Preferred name:

NM_007194.4(CHEK2):c.129del (p.Ser44fs)

HGVS:

NC_000022.11:g.28734594del
NG_008150.2:g.12274del
NM_001005735.2:c.129del
NM_001257387.2:c.-649del
NM_001349956.2:c.129del
NM_007194.4:c.129delMANE SELECT
NM_145862.2:c.129del
NP_001005735.1:p.Ser44fs
NP_001336885.1:p.Ser44fs
NP_009125.1:p.Ser44fs
NP_665861.1:p.Ser44fs
LRG_302t1:c.129del
LRG_302:g.12274del
LRG_302p1:p.Ser44fs
NC_000022.10:g.29130581del
NC_000022.10:g.29130582del

Protein change:

S44fs

Molecular consequence:

NM_001257387.2:c.-649del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001005735.2:c.129del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001349956.2:c.129del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_007194.4:c.129del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_145862.2:c.129del - 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

Recent activity

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Mus musculus hexokinase 3 (Hk3), transcript variant 3, mRNA
Mus musculus hexokinase 3 (Hk3), transcript variant 3, mRNA
gi|329755309|ref|NM_001206391.1|

Nucleotide
Mus musculus B6-derived CD11 +ve dendritic cells cDNA, RIKEN full-length enriche...
Mus musculus B6-derived CD11 +ve dendritic cells cDNA, RIKEN full-length enriched library, clone:F730230B15 product:CD244 natural killer cell receptor 2B4, full insert sequence
gi|74142989|dbj|AK171544.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003212569	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 8, 2022)	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

SCV003212569

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 8, 2022)

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, SCV003212569.2

#	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. 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 creates a premature translational stop signal (p.Ser44Alafs*17) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400).

#	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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