NM_007194.4(CHEK2):c.100C>T (p.Gln34Ter) AND Familial cancer of breast

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 30, 2023
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:: RCV000778091.10

Allele description [Variation Report for NM_007194.4(CHEK2):c.100C>T (p.Gln34Ter)]

NM_007194.4(CHEK2):c.100C>T (p.Gln34Ter)

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.100C>T (p.Gln34Ter)

HGVS:

NC_000022.11:g.28734622G>A
NG_008150.2:g.12245C>T
NM_001005735.2:c.100C>T
NM_001257387.2:c.-678C>T
NM_001349956.2:c.100C>T
NM_007194.4:c.100C>TMANE SELECT
NM_145862.2:c.100C>T
NP_001005735.1:p.Gln34Ter
NP_001336885.1:p.Gln34Ter
NP_009125.1:p.Gln34Ter
NP_665861.1:p.Gln34Ter
LRG_302t1:c.100C>T
LRG_302:g.12245C>T
LRG_302p1:p.Gln34Ter
NC_000022.10:g.29130610G>A
NG_008150.1:g.12213C>T
NM_007194.3:c.100C>T

Protein change:

Q34*

Links:

dbSNP: rs1231012263

NCBI 1000 Genomes Browser:

rs1231012263

Molecular consequence:

NM_001257387.2:c.-678C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001005735.2:c.100C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001349956.2:c.100C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_007194.4:c.100C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_145862.2:c.100C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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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Homo sapiens chromosome 17 open reading frame 101, mRNA (cDNA clone MGC:11111 IM...
Homo sapiens chromosome 17 open reading frame 101, mRNA (cDNA clone MGC:11111 IMAGE:3832978), complete cds
gi|45708388|gb|BC008897.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000914197	Academic Center for Education, Culture and Research, Motamed Cancer Institute	no assertion criteria provided	Pathogenic (May 21, 2019)	germline	clinical testing
SCV000961633	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 30, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21876083, 24713400, 28492532
SCV004043684	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Jun 22, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000914197

Academic Center for Education, Culture and Research, Motamed Cancer Institute

no assertion criteria provided

Pathogenic
(May 21, 2019)

germline

clinical testing

SCV000961633

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 30, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004043684

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Pathogenic
(Jun 22, 2023)

unknown

clinical testing

Citation Link

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	germline	yes	1	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 (3)

Details of each submission

From Academic Center for Education, Culture and Research, Motamed Cancer Institute, SCV000914197.1

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000961633.6

#	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.Gln34*) 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: 491586). 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., SCV004043684.2

#	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 termination codon and is 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

Last Updated: Sep 29, 2024

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