NM_007194.4(CHEK2):c.1036C>T (p.Arg346Cys) AND not provided

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Sep 22, 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:: RCV000212445.15

Allele description [Variation Report for NM_007194.4(CHEK2):c.1036C>T (p.Arg346Cys)]

NM_007194.4(CHEK2):c.1036C>T (p.Arg346Cys)

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.1036C>T (p.Arg346Cys)

Other names:

p.R346C:CGT>TGT

HGVS:

NC_000022.11:g.28696960G>A
NG_008150.2:g.49907C>T
NM_001005735.2:c.1165C>T
NM_001257387.2:c.373C>T
NM_001349956.2:c.835C>T
NM_007194.4:c.1036C>TMANE SELECT
NM_145862.2:c.1009-1087C>T
NP_001005735.1:p.Arg389Cys
NP_001244316.1:p.Arg125Cys
NP_001336885.1:p.Arg279Cys
NP_009125.1:p.Arg346Cys
LRG_302t1:c.1036C>T
LRG_302:g.49907C>T
LRG_302p1:p.Arg346Cys
NC_000022.10:g.29092948G>A
NG_008150.1:g.49875C>T
NM_007194.3:c.1036C>T
p.R346C

Protein change:

R125C

Links:

dbSNP: rs201206424

NCBI 1000 Genomes Browser:

rs201206424

Molecular consequence:

NM_145862.2:c.1009-1087C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001005735.2:c.1165C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001257387.2:c.373C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349956.2:c.835C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_007194.4:c.1036C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV000210979	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 22, 2023)	germline	clinical testing	Citation Link,
SCV001906105	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV001963414	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV004235061	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 19, 2023)	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	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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000210979.18

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

Description

Observed in individuals with breast or ovarian cancer (Zheng et al., 2018; Girard et al., 2019; Krivokuca et al., 2019; Apostolou et al., 2021; Bhai et al., 2021; Fonfria et al., 2021; Gomes et al., 2021; Guindalini et al., 2022); Published functional studies demonstrate a damaging effect: reduced cell growth rate following DNA damage (Delimitsou et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21244692, 26787654, 22114986, 28452373, 30287823, 31050813, 28580595, 30651582, 30303537, 33128190, 34204722, 33925588, 33134171, 27595995, 30851065, 33471991, 30975761, 22419737, 19782031, 36315097, 30130155, 34326862, 36978154, 35441217, 36243179, 35264596)

#	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 Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute - VKGL Data-share Consensus, SCV001906105.1

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

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001963414.1

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

From Revvity Omics, Revvity, SCV004235061.1

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine