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NM_007194.3(CHEK2):c.934A>G (p.Lys312Glu) AND Familial cancer of breast

Clinical significance:Uncertain significance (Last evaluated: Jun 15, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000559307.1

Allele description

NM_007194.3(CHEK2):c.934A>G (p.Lys312Glu)

Gene:
CHEK2:checkpoint kinase 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
22q12.1
Genomic location:
Preferred name:
NM_007194.3(CHEK2):c.934A>G (p.Lys312Glu)
HGVS:
  • NC_000022.11:g.28699912T>C
  • NG_008150.1:g.46923A>G
  • NM_007194.3:c.934A>G
  • NP_009125.1:p.Lys312Glu
  • NC_000022.10:g.29095900T>C
Protein change:
K312E
Links:
dbSNP: rs1064795532
NCBI 1000 Genomes Browser:
rs1064795532
Molecular consequence:
  • NM_007194.3:c.934A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial cancer of breast
Synonyms:
CHEK2-Related Breast Cancer
Identifiers:
MedGen: C0346153; OMIM: 114480

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000633235Invitaecriteria provided, single submitter
Uncertain significance
(Jun 15, 2017)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000633235.1

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

Description

This sequence change replaces lysine with glutamic acid at codon 312 of the CHEK2 protein (p.Lys312Glu). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a CHEK2-related disease. ClinVar contains an entry for this variant (Variation ID: 422065). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on CHEK2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 12, 2018

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