NM_007194.4(CHEK2):c.222del (p.Pro75fs) AND Familial cancer of breast

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 23, 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:: RCV001384270.8

Allele description [Variation Report for NM_007194.4(CHEK2):c.222del (p.Pro75fs)]

NM_007194.4(CHEK2):c.222del (p.Pro75fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

22q12.1

Genomic location:

Preferred name:

NM_007194.4(CHEK2):c.222del (p.Pro75fs)

HGVS:

NC_000022.10:g.29130488del
NC_000022.11:g.28734501del
NG_008150.2:g.12367del
NM_001005735.2:c.222del
NM_001257387.2:c.-556del
NM_001349956.2:c.222del
NM_007194.4:c.222delMANE SELECT
NM_145862.2:c.222del
NP_001005735.1:p.Pro75fs
NP_001336885.1:p.Pro75fs
NP_009125.1:p.Pro75fs
NP_665861.1:p.Pro75fs
LRG_302t1:c.222del
LRG_302:g.12367del
LRG_302p1:p.Pro75fs
NC_000022.10:g.29130488del
NC_000022.10:g.29130488delA
NC_000022.10:g.29130489del

Protein change:

P75fs

Links:

dbSNP: rs2146147030

NCBI 1000 Genomes Browser:

rs2146147030

Molecular consequence:

NM_001257387.2:c.-556del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001005735.2:c.222del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001349956.2:c.222del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_007194.4:c.222del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_145862.2:c.222del - 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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glycosyltransferase 8 domain-containing protein 2 isoform X5 [Dromaius novaeholl...
glycosyltransferase 8 domain-containing protein 2 isoform X5 [Dromaius novaehollandiae]
gi|2718486521|ref|XP_064369786.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001583702	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 5, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21876083, 24713400, 28492532
SCV004044387	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Jun 23, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001583702

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 5, 2022)

germline

clinical testing

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

SCV004044387

Myriad Genetics, Inc.

criteria provided, single submitter

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

Pathogenic
(Jun 23, 2023)

unknown

clinical testing

Citation Link

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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 (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001583702.4

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

Description

ClinVar contains an entry for this variant (Variation ID: 1071738). 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.Pro75Leufs*35) 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). 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., SCV004044387.2

#	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

Last Updated: Sep 29, 2024

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