NM_007194.4(CHEK2):c.106C>T (p.Gln36Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 16, 2021
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:: RCV002413913.2

Allele description [Variation Report for NM_007194.4(CHEK2):c.106C>T (p.Gln36Ter)]

NM_007194.4(CHEK2):c.106C>T (p.Gln36Ter)

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.106C>T (p.Gln36Ter)

HGVS:

NC_000022.11:g.28734616G>A
NG_008150.2:g.12251C>T
NM_001005735.2:c.106C>T
NM_001257387.2:c.-672C>T
NM_001349956.2:c.106C>T
NM_007194.4:c.106C>TMANE SELECT
NM_145862.2:c.106C>T
NP_001005735.1:p.Gln36Ter
NP_001336885.1:p.Gln36Ter
NP_009125.1:p.Gln36Ter
NP_665861.1:p.Gln36Ter
LRG_302t1:c.106C>T
LRG_302:g.12251C>T
LRG_302p1:p.Gln36Ter
NC_000022.10:g.29130604G>A
NM_007194.3:c.106C>T

Protein change:

Q36*

Links:

dbSNP: rs2146151890

NCBI 1000 Genomes Browser:

rs2146151890

Molecular consequence:

NM_001257387.2:c.-672C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001005735.2:c.106C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001349956.2:c.106C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_007194.4:c.106C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_145862.2:c.106C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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
SCV002719253	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jul 16, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002719253

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jul 16, 2021)

germline

clinical testing

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

Citation Link

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

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

Details of each submission

From Ambry Genetics, SCV002719253.2

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

Description

The p.Q36* pathogenic mutation (also known as c.106C>T), located in coding exon 1 of the CHEK2 gene, results from a C to T substitution at nucleotide position 106. This changes the amino acid from a glutamine to a stop codon within coding exon 1. This variant was reported in 0/60,466 breast cancer cases and in 1/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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