NM_007194.4(CHEK2):c.1343T>G (p.Ile448Ser) AND Familial cancer of breast

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: Feb 1, 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:: RCV000203747.19

Allele description [Variation Report for NM_007194.4(CHEK2):c.1343T>G (p.Ile448Ser)]

NM_007194.4(CHEK2):c.1343T>G (p.Ile448Ser)

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.1343T>G (p.Ile448Ser)

Other names:

p.I448S:ATT>AGT

HGVS:

NC_000022.11:g.28695159A>C
NG_008150.2:g.51708T>G
NM_001005735.2:c.1472T>G
NM_001257387.2:c.680T>G
NM_001349956.2:c.1142T>G
NM_007194.4:c.1343T>GMANE SELECT
NM_145862.2:c.1256T>G
NP_001005735.1:p.Ile491Ser
NP_001244316.1:p.Ile227Ser
NP_001336885.1:p.Ile381Ser
NP_009125.1:p.Ile448Ser
NP_665861.1:p.Ile419Ser
LRG_302t1:c.1343T>G
LRG_302:g.51708T>G
LRG_302p1:p.Ile448Ser
NC_000022.10:g.29091147A>C
NG_008150.1:g.51676T>G
NM_001005735.1:c.1472T>G
NM_007194.3:c.1343T>G
O96017:p.Ile448Ser
p.I448S

Protein change:

I227S

Links:

UniProtKB: O96017#VAR_021120; dbSNP: rs17886163

NCBI 1000 Genomes Browser:

rs17886163

Molecular consequence:

NM_001005735.2:c.1472T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001257387.2:c.680T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001349956.2:c.1142T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_007194.4:c.1343T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_145862.2:c.1256T>G - missense variant - [Sequence Ontology: SO:0001583]

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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Mus musculus lactalbumin, alpha (Lalba), mRNA
Mus musculus lactalbumin, alpha (Lalba), mRNA
gi|6754499|ref|NM_010679.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000262385	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Feb 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000488435	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Benign (Mar 28, 2016)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21244692, 24728327 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV004017049	KCCC/NGS Laboratory, Kuwait Cancer Control Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jul 7, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004020180	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely benign (Mar 9, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Rare, evolutionarily unlikely missense substitutions in CHEK2 contribute to breast cancer susceptibility: results from a breast cancer family registry case-control mutation-screening study.

Le Calvez-Kelm F, Lesueur F, Damiola F, Vallée M, Voegele C, Babikyan D, Durand G, Forey N, McKay-Chopin S, Robinot N, Nguyen-Dumont T, Thomas A, Byrnes GB; Breast Cancer Family Registry., Hopper JL, Southey MC, Andrulis IL, John EM, Tavtigian SV.

Breast Cancer Res. 2011 Jan 18;13(1):R6. doi: 10.1186/bcr2810.

PubMed [citation]

PMID:: 21244692
PMCID:: PMC3109572

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000262385.11

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Counsyl, SCV000488435.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	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 KCCC/NGS Laboratory, Kuwait Cancer Control Center, SCV004017049.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004020180.1

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

Description

This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].

#	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

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