NM_007194.4(CHEK2):c.445G>C (p.Glu149Gln) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 27, 2022
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:: RCV002558918.3

Allele description [Variation Report for NM_007194.4(CHEK2):c.445G>C (p.Glu149Gln)]

NM_007194.4(CHEK2):c.445G>C (p.Glu149Gln)

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.445G>C (p.Glu149Gln)

HGVS:

NC_000022.11:g.28725124C>G
NG_008150.2:g.21743G>C
NM_001005735.2:c.574G>C
NM_001257387.2:c.-333G>C
NM_001349956.2:c.444+119G>C
NM_007194.4:c.445G>CMANE SELECT
NM_145862.2:c.445G>C
NP_001005735.1:p.Glu192Gln
NP_009125.1:p.Glu149Gln
NP_665861.1:p.Glu149Gln
LRG_302t1:c.445G>C
LRG_302:g.21743G>C
LRG_302p1:p.Glu149Gln
NC_000022.10:g.29121112C>G
NC_000022.10:g.29121112C>G
NG_008150.1:g.21711G>C
NM_007194.3:c.445G>C

Protein change:

E149Q

Links:

dbSNP: rs587782560

NCBI 1000 Genomes Browser:

rs587782560

Molecular consequence:

NM_001257387.2:c.-333G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001349956.2:c.444+119G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001005735.2:c.574G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_007194.4:c.445G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_145862.2:c.445G>C - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003244113	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 27, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003244113

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 27, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003244113.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

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. This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 149 of the CHEK2 protein (p.Glu149Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 920756). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine