U.S. flag

An official website of the United States government

NM_007194.4(CHEK2):c.194C>G (p.Thr65Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Apr 16, 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:
RCV000777678.8

Allele description [Variation Report for NM_007194.4(CHEK2):c.194C>G (p.Thr65Arg)]

NM_007194.4(CHEK2):c.194C>G (p.Thr65Arg)

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.194C>G (p.Thr65Arg)
HGVS:
  • NC_000022.11:g.28734528G>C
  • NG_008150.2:g.12339C>G
  • NM_001005735.2:c.194C>G
  • NM_001257387.2:c.-584C>G
  • NM_001349956.2:c.194C>G
  • NM_007194.4:c.194C>GMANE SELECT
  • NM_145862.2:c.194C>G
  • NP_001005735.1:p.Thr65Arg
  • NP_001336885.1:p.Thr65Arg
  • NP_009125.1:p.Thr65Arg
  • NP_665861.1:p.Thr65Arg
  • LRG_302t1:c.194C>G
  • LRG_302:g.12339C>G
  • LRG_302p1:p.Thr65Arg
  • NC_000022.10:g.29130516G>C
  • NG_008150.1:g.12307C>G
  • NM_007194.3:c.194C>G
Protein change:
T65R
Links:
dbSNP: rs864622684
NCBI 1000 Genomes Browser:
rs864622684
Molecular consequence:
  • NM_001257387.2:c.-584C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001005735.2:c.194C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349956.2:c.194C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007194.4:c.194C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_145862.2:c.194C>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

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000913605Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jul 31, 2018) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001174340Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Apr 16, 2024) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

ENIGMA CHEK2gether Project: A Comprehensive Study Identifies Functionally Impaired CHEK2 Germline Missense Variants Associated with Increased Breast Cancer Risk.

Stolarova L, Kleiblova P, Zemankova P, Stastna B, Janatova M, Soukupova J, Achatz MI, Ambrosone C, Apostolou P, Arun BK, Auer P, Barnard M, Bertelsen B; Biobank Japan., Blok MJ, Boddicker N, Brunet J, Burnside ES, Calvello M, Campbell I, Chan SH, Chen F, et al.

Clin Cancer Res. 2023 Aug 15;29(16):3037-3050. doi: 10.1158/1078-0432.CCR-23-0212.

PubMed [citation]
PMID:
37449874
PMCID:
PMC10425727

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000913605.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Ambry Genetics, SCV001174340.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The p.T65R variant (also known as c.194C>G), located in coding exon 1 of the CHEK2 gene, results from a C to G substitution at nucleotide position 194. The threonine at codon 65 is replaced by arginine, an amino acid with similar properties. This alteration was reported as functional in a study assessing CHEK2-complementation through quantification of KAP1 phosphorylation and CHK2 autophosphorylation in human RPE1-CHEK2-knockout cells (Stolarova L et al. Clin Cancer Res, 2023 Aug;29:3037-3050). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024