NM_007194.4(CHEK2):c.1111_1127dup (p.Glu377fs) AND Familial cancer of breast

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Jan 5, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002249759.8

Allele description [Variation Report for NM_007194.4(CHEK2):c.1111_1127dup (p.Glu377fs)]

NM_007194.4(CHEK2):c.1111_1127dup (p.Glu377fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

22q12.1

Genomic location:

Preferred name:

NM_007194.4(CHEK2):c.1111_1127dup (p.Glu377fs)

HGVS:

NC_000022.11:g.28695851_28695867dup
NG_008150.2:g.51009_51025dup
NM_001005735.2:c.1240_1256dup
NM_001257387.2:c.448_464dup
NM_001349956.2:c.910_926dup
NM_007194.4:c.1111_1127dupMANE SELECT
NM_145862.2:c.1024_1040dup
NP_001005735.1:p.Glu420fs
NP_001244316.1:p.Glu156fs
NP_001336885.1:p.Glu310fs
NP_009125.1:p.Glu377fs
NP_665861.1:p.Glu348fs
LRG_302t1:c.1111_1127dup
LRG_302:g.51009_51025dup
LRG_302p1:p.Glu377fs
NC_000022.10:g.29091829_29091830insCCCAAAATCTTGGAGTG
NC_000022.10:g.29091839_29091855dup
NC_000022.11:g.28695841_28695842insCCCAAAATCTTGGAGTG
NG_008150.1:g.50977_50993dup
NM_007194.3:c.1111_1127dup
NM_007194.3:c.1111_1127dupCACTCCAAGATTTTGGG

Protein change:

E156fs

Links:

dbSNP: rs2052563898

NCBI 1000 Genomes Browser:

rs2052563898

Molecular consequence:

NM_001005735.2:c.1240_1256dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001257387.2:c.448_464dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001349956.2:c.910_926dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_007194.4:c.1111_1127dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_145862.2:c.1024_1040dup - 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

Clear Turn Off Turn On

Homo sapiens hypothetical LOC283050, mRNA (cDNA clone IMAGE:40024415)
Homo sapiens hypothetical LOC283050, mRNA (cDNA clone IMAGE:40024415)
gi|114205519|gb|BC105703.1|

Nucleotide
JGI_CAAR2177.fwd NIH_XGC_tropLiv1 Xenopus tropicalis cDNA clone IMAGE:7734428 5'...
JGI_CAAR2177.fwd NIH_XGC_tropLiv1 Xenopus tropicalis cDNA clone IMAGE:7734428 5', mRNA sequence
gi|58863423|gnl|dbEST|27730020|gb|D 89.1|

Nucleotide
EC0CAA002DG09.g1 Xenopus tropicalis xthr plasmid library Xenopus tropicalis cDNA...
EC0CAA002DG09.g1 Xenopus tropicalis xthr plasmid library Xenopus tropicalis cDNA clone xthr02N18 5', mRNA sequence
gi|45912584|gnl|dbEST|22233077|gb|C 88.1|

Nucleotide
AL682264 XGC-gastrula Xenopus tropicalis cDNA clone TGas058k20 5', mRNA sequence
AL682264 XGC-gastrula Xenopus tropicalis cDNA clone TGas058k20 5', mRNA sequence
gi|38254070|gnl|dbEST|20351523|emb| 264.2|

Nucleotide
JGI_CAAK11047.rev NIH_XGC_tropBrn3 Xenopus tropicalis cDNA clone IMAGE:7661764 3...
JGI_CAAK11047.rev NIH_XGC_tropBrn3 Xenopus tropicalis cDNA clone IMAGE:7661764 3', mRNA sequence
gi|71606876|gnl|dbEST|30437248|gb|C 96.2|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002518703	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2019)	Pathogenic (May 4, 2022)	germline	clinical testing	Citation Link,
SCV003017582	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 5, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21876083, 24713400, 28492532
SCV004044531	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Jun 28, 2023)	unknown	clinical testing	Citation Link,
SCV004217696	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 30, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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
not provided	unknown	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 (4)

Details of each submission

From Mendelics, SCV002518703.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003017582.2

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

Description

This sequence change creates a premature translational stop signal (p.Glu377Thrfs*11) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 920804). For these reasons, this variant has been classified as Pathogenic.

#	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

From Myriad Genetics, Inc., SCV004044531.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004217696.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

ClinVar

Relating variation to medicine