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NM_007194.4(CHEK2):c.1568G>A (p.Arg523His) AND Familial cancer of breast

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 5, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000546521.11

Allele description [Variation Report for NM_007194.4(CHEK2):c.1568G>A (p.Arg523His)]

NM_007194.4(CHEK2):c.1568G>A (p.Arg523His)

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.1568G>A (p.Arg523His)
HGVS:
  • NC_000022.11:g.28687961C>T
  • NG_008150.2:g.58906G>A
  • NM_001005735.2:c.1697G>A
  • NM_001257387.2:c.905G>A
  • NM_001349956.2:c.1367G>A
  • NM_007194.4:c.1568G>AMANE SELECT
  • NM_145862.2:c.1481G>A
  • NP_001005735.1:p.Arg566His
  • NP_001244316.1:p.Arg302His
  • NP_001336885.1:p.Arg456His
  • NP_009125.1:p.Arg523His
  • NP_665861.1:p.Arg494His
  • LRG_302t1:c.1568G>A
  • LRG_302:g.58906G>A
  • LRG_302p1:p.Arg523His
  • NC_000022.10:g.29083949C>T
  • NG_008150.1:g.58874G>A
  • NM_007194.3:c.1568G>A
Protein change:
R302H
Links:
dbSNP: rs948928965
NCBI 1000 Genomes Browser:
rs948928965
Molecular consequence:
  • NM_001005735.2:c.1697G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257387.2:c.905G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349956.2:c.1367G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007194.4:c.1568G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_145862.2:c.1481G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial cancer of breast
Synonyms:
Breast cancer, familial; Hereditary breast cancer
Identifiers:
MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000633148Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 5, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations.

Tsaousis GN, Papadopoulou E, Apessos A, Agiannitopoulos K, Pepe G, Kampouri S, Diamantopoulos N, Floros T, Iosifidou R, Katopodi O, Koumarianou A, Markopoulos C, Papazisis K, Venizelos V, Xanthakis I, Xepapadakis G, Banu E, Eniu DT, Negru S, Stanculeanu DL, Ungureanu A, Ozmen V, et al.

BMC Cancer. 2019 Jun 3;19(1):535. doi: 10.1186/s12885-019-5756-4.

PubMed [citation]
PMID:
31159747
PMCID:
PMC6547505

The CHK2 kinase is recurrently mutated and functionally impaired in the germline of pediatric cancer patients.

Wagener R, Walter C, Auer F, Alzoubi D, Hauer J, Fischer U, Varghese J, Dugas M, Borkhardt A, Brozou T.

Int J Cancer. 2023 Apr 1;152(7):1388-1398. doi: 10.1002/ijc.34390. Epub 2022 Dec 27.

PubMed [citation]
PMID:
36468172
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000633148.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 523 of the CHEK2 protein (p.Arg523His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with personal or family history of breast and/or ovarian cancer and pediatric neuroectodermal tumor (PMID: 31159747, 36468172). ClinVar contains an entry for this variant (Variation ID: 460810). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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

Last Updated: Sep 29, 2024