NM_007194.4(CHEK2):c.134C>T (p.Thr45Met) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 10, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000523789.11

Allele description [Variation Report for NM_007194.4(CHEK2):c.134C>T (p.Thr45Met)]

NM_007194.4(CHEK2):c.134C>T (p.Thr45Met)

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.134C>T (p.Thr45Met)

HGVS:

NC_000022.11:g.28734588G>A
NG_008150.2:g.12279C>T
NM_001005735.2:c.134C>T
NM_001257387.2:c.-644C>T
NM_001349956.2:c.134C>T
NM_007194.4:c.134C>TMANE SELECT
NM_145862.2:c.134C>T
NP_001005735.1:p.Thr45Met
NP_001336885.1:p.Thr45Met
NP_009125.1:p.Thr45Met
NP_665861.1:p.Thr45Met
LRG_302t1:c.134C>T
LRG_302:g.12279C>T
LRG_302p1:p.Thr45Met
NC_000022.10:g.29130576G>A
NG_008150.1:g.12247C>T
NM_007194.3:c.134C>T

Protein change:

T45M

Links:

dbSNP: rs558321010

NCBI 1000 Genomes Browser:

rs558321010

Molecular consequence:

NM_001257387.2:c.-644C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001005735.2:c.134C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349956.2:c.134C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_007194.4:c.134C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_145862.2:c.134C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV000618417	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 10, 2024)	germline	clinical testing	Citation Link,
SCV004221724	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jan 18, 2023)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 33471991, 28944238, 26580448, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000618417

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Sep 10, 2024)

germline

clinical testing

Citation Link,

SCV004221724

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jan 18, 2023)

unknown

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium., Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]

PMID:: 33471991
PMCID:: PMC7611105

Targeted sequencing of 36 known or putative colorectal cancer susceptibility genes.

DeRycke MS, Gunawardena S, Balcom JR, Pickart AM, Waltman LA, French AJ, McDonnell S, Riska SM, Fogarty ZC, Larson MC, Middha S, Eckloff BW, Asmann YW, Ferber MJ, Haile RW, Gallinger S, Clendenning M, Rosty C, Win AK, Buchanan DD, Hopper JL, Newcomb PA, et al.

Mol Genet Genomic Med. 2017 Sep;5(5):553-569. doi: 10.1002/mgg3.317.

PubMed [citation]

PMID:: 28944238
PMCID:: PMC5606870

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000618417.8

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

Description

Observed in individuals with breast, colorectal, prostate or other cancers and also in unaffected controls (PMID: 26580448, 27498913, 28944238, 32832836, 33471991, 32546565, 37449874); Published functional studies suggest a neutral effect: auto-phosphorylation and kinase activity comparable to wild type (PMID: 37449874); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24448499, 27498913, 26580448, 28944238, 32832836, 33471991, 32546565, 37449874, 11733767, 22114986)

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004221724.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The frequency of this variant in the general population, 0.00012 (3/24932 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals with colorectal cancer (PMID: 28944238 (2017)) and acute lymphoblastic leukemia (PMID: 26580448 (2015)). In a large scale breast cancer association study, the variant was observed in breast cancer cases as well as in control subjects (see LOVD (http://databases.lovd.nl/shared/genes/CHEK2) and PMID: 33471991 (2021)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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

Last Updated: Oct 8, 2024

ClinVar

Relating variation to medicine