NM_007194.4(CHEK2):c.1534C>G (p.Leu512Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Oct 18, 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:: RCV000130543.16

Allele description [Variation Report for NM_007194.4(CHEK2):c.1534C>G (p.Leu512Val)]

NM_007194.4(CHEK2):c.1534C>G (p.Leu512Val)

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.1534C>G (p.Leu512Val)

HGVS:

NC_000022.11:g.28689143G>C
NG_008150.2:g.57724C>G
NM_001005735.2:c.1663C>G
NM_001257387.2:c.871C>G
NM_001349956.2:c.1333C>G
NM_007194.4:c.1534C>GMANE SELECT
NM_145862.2:c.1447C>G
NP_001005735.1:p.Leu555Val
NP_001244316.1:p.Leu291Val
NP_001336885.1:p.Leu445Val
NP_009125.1:p.Leu512Val
NP_665861.1:p.Leu483Val
LRG_302t1:c.1534C>G
LRG_302:g.57724C>G
LRG_302p1:p.Leu512Val
NC_000022.10:g.29085131G>C
NG_008150.1:g.57692C>G
NM_007194.3:c.1534C>G
O96017:p.Leu512Val
p.L512V

Protein change:

L291V

Links:

UniProtKB: O96017#VAR_021122; dbSNP: rs17882942

NCBI 1000 Genomes Browser:

rs17882942

Molecular consequence:

NM_001005735.2:c.1663C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001257387.2:c.871C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001349956.2:c.1333C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_007194.4:c.1534C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_145862.2:c.1447C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000185412	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Oct 18, 2024)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 21244692, 26787654, 28944238, 30851065, 31206626, 35643632, 37449874 Citation Link,
SCV000911101	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jun 28, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000185412

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Oct 18, 2024)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link,

SCV000911101

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jun 28, 2016)

germline

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

Citations

PubMed

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

Multigene testing of moderate-risk genes: be mindful of the missense.

Young EL, Feng BJ, Stark AW, Damiola F, Durand G, Forey N, Francy TC, Gammon A, Kohlmann WK, Kaphingst KA, McKay-Chopin S, Nguyen-Dumont T, Oliver J, Paquette AM, Pertesi M, Robinot N, Rosenthal JS, Vallee M, Voegele C, Hopper JL, Southey MC, Andrulis IL, et al.

J Med Genet. 2016 Jun;53(6):366-76. doi: 10.1136/jmedgenet-2015-103398. Epub 2016 Jan 19.

PubMed [citation]

PMID:: 26787654
PMCID:: PMC4893078

See all PubMed Citations (8)

Details of each submission

From Ambry Genetics, SCV000185412.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000911101.1

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

Last Updated: Jan 19, 2025

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