NM_007194.4(CHEK2):c.1078G>A (p.Glu360Lys) AND Familial cancer of breast

Clinical significance:Uncertain significance (Last evaluated: Oct 16, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000233648.8

Allele description [Variation Report for NM_007194.4(CHEK2):c.1078G>A (p.Glu360Lys)]

NM_007194.4(CHEK2):c.1078G>A (p.Glu360Lys)

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.1078G>A (p.Glu360Lys)
HGVS:
  • NC_000022.11:g.28696918C>T
  • NG_008150.1:g.49917G>A
  • NG_008150.2:g.49949G>A
  • NM_001005735.2:c.1207G>A
  • NM_001257387.2:c.415G>A
  • NM_001349956.2:c.877G>A
  • NM_007194.4:c.1078G>AMANE SELECT
  • NM_145862.2:c.1009-1045G>A
  • NP_001005735.1:p.Glu403Lys
  • NP_001244316.1:p.Glu139Lys
  • NP_001336885.1:p.Glu293Lys
  • NP_009125.1:p.Glu360Lys
  • LRG_302t1:c.1078G>A
  • LRG_302:g.49949G>A
  • LRG_302p1:p.Glu360Lys
  • NC_000022.10:g.29092906C>T
  • NM_007194.3:c.1078G>A
Protein change:
E139K
Links:
dbSNP: rs876658337
NCBI 1000 Genomes Browser:
rs876658337
Molecular consequence:
  • NM_145862.2:c.1009-1045G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001005735.2:c.1207G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257387.2:c.415G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349956.2:c.877G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007194.4:c.1078G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial cancer of breast
Synonyms:
Breast cancer, familial; CHEK2-Related Breast Cancer
Identifiers:
MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000289643Invitaecriteria provided, single submitter
Uncertain significance
(Oct 16, 2020)
germlineclinical testing

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

SCV000785314Counsylcriteria provided, single submitter
Uncertain significance
(Jul 5, 2017)
unknownclinical testing

Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot 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, SCV000289643.8

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

Description

This sequence change replaces glutamic acid with lysine at codon 360 of the CHEK2 protein (p.Glu360Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CHEK2-related disease. ClinVar contains an entry for this variant (Variation ID: 230025). 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, the available evidence is currently insufficient to determine the role of this variant 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

From Counsyl, SCV000785314.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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