NM_007194.4(CHEK2):c.319G>A (p.Glu107Lys) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 10, 2024
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:: RCV001062326.10

Allele description [Variation Report for NM_007194.4(CHEK2):c.319G>A (p.Glu107Lys)]

NM_007194.4(CHEK2):c.319G>A (p.Glu107Lys)

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.319G>A (p.Glu107Lys)

HGVS:

NC_000022.11:g.28734403C>T
NG_008150.2:g.12464G>A
NM_001005735.2:c.319G>A
NM_001257387.2:c.-459G>A
NM_001349956.2:c.319G>A
NM_007194.4:c.319G>AMANE SELECT
NM_145862.2:c.319G>A
NP_001005735.1:p.Glu107Lys
NP_001336885.1:p.Glu107Lys
NP_009125.1:p.Glu107Lys
NP_665861.1:p.Glu107Lys
LRG_302t1:c.319G>A
LRG_302:g.12464G>A
LRG_302p1:p.Glu107Lys
NC_000022.10:g.29130391C>T
NG_008150.1:g.12432G>A
NM_007194.3:c.319G>A

Protein change:

E107K

Links:

dbSNP: rs775320614

NCBI 1000 Genomes Browser:

rs775320614

Molecular consequence:

NM_001257387.2:c.-459G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001005735.2:c.319G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349956.2:c.319G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_007194.4:c.319G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_145862.2:c.319G>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

Recent activity

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cruciferin (DUF506) [Arabidopsis thaliana]
cruciferin (DUF506) [Arabidopsis thaliana]
gi|15225517|ref|NP_181495.1|

Protein
Gm17911 AND (alive[prop]) (2)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001227120	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 10, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 30303537, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001227120

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 10, 2024)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Familial breast cancer and DNA repair genes: Insights into known and novel susceptibility genes from the GENESIS study, and implications for multigene panel testing.

Girard E, Eon-Marchais S, Olaso R, Renault AL, Damiola F, Dondon MG, Barjhoux L, Goidin D, Meyer V, Le Gal D, Beauvallet J, Mebirouk N, Lonjou C, Coignard J, Marcou M, Cavaciuti E, Baulard C, Bihoreau MT, Cohen-Haguenauer O, Leroux D, Penet C, Fert-Ferrer S, et al.

Int J Cancer. 2019 Apr 15;144(8):1962-1974. doi: 10.1002/ijc.31921. Epub 2018 Nov 13.

PubMed [citation]

PMID:: 30303537
PMCID:: PMC6587727

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001227120.5

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

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 107 of the CHEK2 protein (p.Glu107Lys). This variant also falls at the last nucleotide of exon 2, which is part of the consensus splice site for this exon. This variant is present in population databases (rs775320614, gnomAD 0.003%). This missense change has been observed in individual(s) with breast cancer (PMID: 30303537). ClinVar contains an entry for this variant (Variation ID: 856789). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

#	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

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