NM_007194.4(CHEK2):c.1118A>G (p.Lys373Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 18, 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:: RCV000165259.10

Allele description [Variation Report for NM_007194.4(CHEK2):c.1118A>G (p.Lys373Arg)]

NM_007194.4(CHEK2):c.1118A>G (p.Lys373Arg)

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.1118A>G (p.Lys373Arg)

HGVS:

NC_000022.11:g.28695851T>C
NG_008150.2:g.51016A>G
NM_001005735.2:c.1247A>G
NM_001257387.2:c.455A>G
NM_001349956.2:c.917A>G
NM_007194.4:c.1118A>GMANE SELECT
NM_145862.2:c.1031A>G
NP_001005735.1:p.Lys416Arg
NP_001244316.1:p.Lys152Arg
NP_001336885.1:p.Lys306Arg
NP_009125.1:p.Lys373Arg
NP_665861.1:p.Lys344Arg
LRG_302t1:c.1118A>G
LRG_302:g.51016A>G
LRG_302p1:p.Lys373Arg
NC_000022.10:g.29091839T>C
NG_008150.1:g.50984A>G
NM_007194.3:c.1118A>G
p.K373R

Protein change:

K152R

Links:

dbSNP: rs786202446

NCBI 1000 Genomes Browser:

rs786202446

Molecular consequence:

NM_001005735.2:c.1247A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001257387.2:c.455A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001349956.2:c.917A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_007194.4:c.1118A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_145862.2:c.1031A>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

Recent activity

Clear Turn Off Turn On

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
SCV000215975	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jan 18, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25186627, 30851065 Citation Link,
SCV000684561	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 31, 2018)	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

SCV000215975

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jan 18, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000684561

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 31, 2018)

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

Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.

Tung N, Battelli C, Allen B, Kaldate R, Bhatnagar S, Bowles K, Timms K, Garber JE, Herold C, Ellisen L, Krejdovsky J, DeLeonardis K, Sedgwick K, Soltis K, Roa B, Wenstrup RJ, Hartman AR.

Cancer. 2015 Jan 1;121(1):25-33. doi: 10.1002/cncr.29010. Epub 2014 Sep 3.

PubMed [citation]

PMID:: 25186627

Functional characterization of CHEK2 variants in a Saccharomyces cerevisiae system.

Delimitsou A, Fostira F, Kalfakakou D, Apostolou P, Konstantopoulou I, Kroupis C, Papavassiliou AG, Kleibl Z, Stratikos E, Voutsinas GE, Yannoukakos D.

Hum Mutat. 2019 May;40(5):631-648. doi: 10.1002/humu.23728. Epub 2019 Mar 9.

PubMed [citation]

PMID:: 30851065

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000215975.8

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

Description

The p.K373R variant (also known as c.1118A>G), located in coding exon 10 of the CHEK2 gene, results from an A to G substitution at nucleotide position 1118. The lysine at codon 373 is replaced by arginine, an amino acid with highly similar properties. This variant was detected on a 25-gene panel test in a woman of mixed ancestry who was diagnosed with breast cancer before age 50 (Tung N et al. Cancer, 2015 Jan;121:25-33). In another study, this alteration behaved as functional in an in vivo, yeast-based growth rate assay (Delimitsou A et al. Hum. Mutat., 2019 05;40:631-648). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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, SCV000684561.2

#	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: May 1, 2024

ClinVar

Relating variation to medicine