NM_007194.3(CHEK2):c.190G>A (p.Glu64Lys) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Mar 15, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description

NM_007194.3(CHEK2):c.190G>A (p.Glu64Lys)

CHEK2:checkpoint kinase 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_007194.3(CHEK2):c.190G>A (p.Glu64Lys)
Other names:
  • NC_000022.11:g.28734532C>T
  • NG_008150.1:g.12303G>A
  • NM_001257387.1:c.-588G>A
  • NM_007194.3:c.190G>A
  • NP_009125.1:p.Glu64Lys
  • NC_000022.10:g.29130520C>T
  • O96017:p.Glu64Lys
  • p.E64K
Protein change:
UniProtKB: O96017#VAR_019107; dbSNP: rs141568342
NCBI 1000 Genomes Browser:
Allele Frequency:
Molecular consequence:
  • NM_001257387.1:c.-588G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_007194.3:c.190G>A - missense variant - [Sequence Ontology: SO:0001583]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000149918GeneDxcriteria provided, single submitter
Likely pathogenic
(Mar 15, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000149918.12

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


This variant is denoted CHEK2 c.190G>A at the cDNA level, p.Glu64Lys (E64K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAG>AAG). This variant has been reported in individuals with personal and/or family history of breast, prostate, or pancreatic cancer (Dong 2003, Wu 2006, Desrichard 2011, Roeb 2012, Shirts 2016, Tung 2016). Functional analyses have shown reduced phosphorylation and kinase activity as well as loss of DNA damage response (Wu 2006, Roeb 2012). CHEK2 Glu64Lys was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Glutamic Acid and Lysine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. This variant occurs at a position where amino acids with properties similar to Glutamic Acid are tolerated across species and is located in the SQ/TQ domain (Desrichard 2011, Roeb 2012). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, we consider CHEK2 Glu64Lys to be a likely pathogenic variant.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 11, 2017

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