ClinVar Genomic variation as it relates to human health
NM_007194.4(CHEK2):c.349A>G (p.Arg117Gly)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007194.4(CHEK2):c.349A>G (p.Arg117Gly)
Variation ID: 128071 Accession: VCV000128071.94
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 22q12.1 22: 28725338 (GRCh38) [ NCBI UCSC ] 22: 29121326 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 16, 2017 Aug 25, 2024 Mar 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007194.4:c.349A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009125.1:p.Arg117Gly missense NM_001005735.2:c.478A>G NP_001005735.1:p.Arg160Gly missense NM_001257387.2:c.-429A>G 5 prime UTR NM_001349956.2:c.349A>G NP_001336885.1:p.Arg117Gly missense NM_145862.2:c.349A>G NP_665861.1:p.Arg117Gly missense NC_000022.11:g.28725338T>C NC_000022.10:g.29121326T>C NG_008150.2:g.21529A>G LRG_302:g.21529A>G LRG_302t1:c.349A>G LRG_302p1:p.Arg117Gly O96017:p.Arg117Gly - Protein change
- R117G, R160G
- Other names
- p.R117G:AGG>GGG
- Canonical SPDI
- NC_000022.11:28725337:T:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
The Genome Aggregation Database (gnomAD) 0.00009
Trans-Omics for Precision Medicine (TOPMed) 0.00011
The Genome Aggregation Database (gnomAD), exomes 0.00012
Exome Aggregation Consortium (ExAC) 0.00013
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CHEK2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
4045 | 4100 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Dec 5, 2023 | RCV000116012.25 | |
Pathogenic/Likely pathogenic (9) |
criteria provided, multiple submitters, no conflicts
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Mar 29, 2024 | RCV000204429.29 | |
Pathogenic/Likely pathogenic (16) |
criteria provided, multiple submitters, no conflicts
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Feb 6, 2024 | RCV000212414.52 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 12, 2018 | RCV001258041.5 | |
Predisposition to cancer
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Likely pathogenic (1) |
criteria provided, single submitter
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May 13, 2021 | RCV001526815.6 |
Pathogenic (2) |
criteria provided, single submitter
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Jun 9, 2022 | RCV001263516.8 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Aug 1, 2020 | RCV001374534.5 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 6, 2023 | RCV001787918.7 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jan 18, 2023 | RCV001798355.7 | |
CHEK2-related disorder
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Pathogenic (1) |
criteria provided, single submitter
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Oct 3, 2022 | RCV003114263.7 |
Likely pathogenic (1) |
criteria provided, single submitter
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Dec 8, 2021 | RCV002498498.4 | |
Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 25, 2022 | RCV004556728.2 | |
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Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(May 25, 2021)
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criteria provided, single submitter
Method: clinical testing
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Li-Fraumeni syndrome 2
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Study: CSER-TexasKidsCanSeq
Accession: SCV002030095.1 First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021 |
Comment:
This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
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Likely pathogenic
(Oct 30, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002537425.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The CHEK2 c.349A>G (p.R117G) variant has been reported in heterozygosity in numerous individuals with different types of cancer, including breast, colon, ovarian, pancreatic, prostate, and … (more)
The CHEK2 c.349A>G (p.R117G) variant has been reported in heterozygosity in numerous individuals with different types of cancer, including breast, colon, ovarian, pancreatic, prostate, and others (PMID: 12454775, 26681312, 30067863, 30322717, 31206626, 32906215, 21244692, 33326660). This variant was also identified in healthy controls (PMID: 32906215, 21244692). Functional studies have shown that this variant reduces the kinase activity (PMID: 18725978, 16835864). This variant was observed in 24/128958 chromosomes in the Non-Finnish European population, with no homozygotes, according to the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). This variant has been reported in ClinVar (Variation ID: 128071). Based on the current evidence available, this variant is interpreted as likely pathogenic. (less)
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Pathogenic
(Jun 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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Malignant tumor of breast
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698796.5
First in ClinVar: Feb 19, 2018 Last updated: Aug 03, 2022 |
Comment:
Variant summary: CHEK2 c.349A>G (p.Arg117Gly) results in a non-conservative amino acid change located in the Forkhead-associated (FHA) domain (IPR000253) of the encoded protein sequence. Five … (more)
Variant summary: CHEK2 c.349A>G (p.Arg117Gly) results in a non-conservative amino acid change located in the Forkhead-associated (FHA) domain (IPR000253) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. This variant allele was found in 33/265114 control chromosomes at a frequency of 0.00012 (gnomAD and publications). This frequency is not higher than expected for a pathogenic variant in CHEK2 causing Breast Cancer (0.00012 vs 0.00031), allowing no conclusion about variant significance. The variant, c.349A>G, has been reported in the literature in multiple individuals affected with cancer including breast cancer, pancreatic cancer, colorectal cancer and prostate cancer (but also in controls) (Hu_2018, Lu_2018, Martin-Morales_2018, Paulo_2018, Rummel_2017, Pinto_2016, Southey_2016), with limited cosegregation information. In one study, in 3 families, 8 transmissions of the variant allele and 2 transmissions of the reference allele to affected individuals was reported (Schutte_2003). The variant has also been reported in studies that included cohorts of comprehensively genotyped patients with early onset breast cancer meeting the NCCN guidelines (Rummel_2017), and a family history of breast cancer (Pinto_2016; Moran_2017, Lu_2018). A case-control study showed evidence of association with breast cancer (OR = 2.03; Southey_2016) but no association with prostate and ovarian cancer, suggesting this might be a risk variant. FLOSSIES database reports the variant in 2 women older than age 70 years who have never had cancer. In addition, co-occurrences with other pathogenic variants have been reported (BRCA2 c.891_899delAACAGTTGTinsGATACTTCAG, p.Thr298Ilefs; CHEK2 c.1100delC, p.Thr367fsX15 (Susswein_2015); APC c.426_427delAT, p.Leu143AlafsX4 at our laboratory). However, as co-occurrence with other pathogenic variants is not mutually exclusive in cancer probands, this is not entirely supportive of a benign role of this variant. Functional in vitro and in vivo studies showed that p.R117G is incompletely phosphorylated and is not efficiently activated in response to DNA damage, showing minimal kinase activity when studied in isolation, however, it can dimerize efficiently to CHEK2 wild-type without strongly affecting the wild-type CHEK2 activity (Roeb_2012, Chrisanthar_2008, Sodha_2006, Wu_2006). Twenty ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely pathogenic (n=16) and pathogenic (n=4). Several submitters cite overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Likely pathogenic
(Feb 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000677766.2
First in ClinVar: Jan 06, 2018 Last updated: Dec 24, 2022 |
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Pathogenic
(Oct 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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CHEK2-related disorder
Affected status: unknown
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV003799122.2
First in ClinVar: Feb 13, 2023 Last updated: Mar 04, 2023 |
Comment:
PS3, PS4, PP3
Secondary finding: yes
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Likely pathogenic
(Mar 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004215845.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Likely pathogenic
(Sep 08, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000806879.1
First in ClinVar: Sep 13, 2018 Last updated: Sep 13, 2018 |
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Likely pathogenic
(Apr 02, 2020)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: yes
Allele origin:
germline
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Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499647.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
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Likely pathogenic
(May 13, 2021)
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criteria provided, single submitter
Method: clinical testing
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Predisposition to cancer
Affected status: unknown
Allele origin:
germline
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St. Jude Molecular Pathology, St. Jude Children's Research Hospital
Accession: SCV001737462.2
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
Comment:
The CHEK2 c.349A>G (p.Arg117Gly) missense change has a maximum frequency of 0.019% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/22-29121326-T-C?dataset=gnomad_r2_1). Seven of seven in silico tools predict a deleterious … (more)
The CHEK2 c.349A>G (p.Arg117Gly) missense change has a maximum frequency of 0.019% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/22-29121326-T-C?dataset=gnomad_r2_1). Seven of seven in silico tools predict a deleterious effect of this variant on protein function (PP3). Several functional studies suggest that this variant is pathogenic, demonstrating a strongly reduced CHEK2-mediated DNA damage response, impaired kinase activity, and incomplete phosphorylation (PS3; PMID: 18725978, 22419737, 30851065, 16835864, 16982735). This variant has been identified in many cancer cases including familial breast/ovarian, prostate, pancreatic, colorectal, as well as other cancer types (PMID: 12454775, 15095295, 21244692, 26681312, 28125075, 29439820, 29659569, 29439820, 29945567, 30322717, 30256826, 28709830, 30426508, 31090900, 31263054, 31206626, 32906215, 30676620, 32906215). A case-control study showed evidence of association with breast cancer (PS4; OR = 2.26; PMID: 27595995), but no association with prostate and ovarian cancer. In addition, the variant segregated with breast cancer in three families, although it was not identified in all affected family members (PMID: 12610780) This variant is present 2x in the FLOSSIES database which contains genetic variants from women older than 70 years of age who have never had cancer (BS2_supporting; https://whi.color.com/). In summary, this variant meets criteria to be classified as likely pathogenic based on the ACMG/AMP criteria: PS3, PS4, PP3, BS2_supporting. (less)
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Likely pathogenic
(Apr 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002761585.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
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Likely pathogenic
(Dec 08, 2021)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Colorectal cancer Familial prostate cancer Bone osteosarcoma Li-Fraumeni syndrome 2
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002806805.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Dec 30, 2019)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000149921.17
First in ClinVar: May 17, 2014 Last updated: Mar 04, 2023 |
Comment:
Published functional studies demonstrate a damaging effect: reduced auto-phosphorylation, protein instability, impaired kinase activity, and loss of CHEK2-mediated DNA damage response (Wu 2006, Sodha 2006, … (more)
Published functional studies demonstrate a damaging effect: reduced auto-phosphorylation, protein instability, impaired kinase activity, and loss of CHEK2-mediated DNA damage response (Wu 2006, Sodha 2006, Chrisanthar 2008, Roeb 2012, Delimitsou 2019); Case control study in Europeans suggests this variant is associated with female breast cancer (Southey 2016); Observed in many individuals with CHEK2-related cancers (Sodha 2002, Kleibl 2008, Desrichard 2011, Le Calvez-Kelm 2011, Roeb 2012, Castera 2014, Moran 2017, Pinto 2016, Lu 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 12454775, 18058223, 22114986, 21244692, 22419737, 24549055, 27798748, 27553368, 30128536, 27595995, 16835864, 16982735, 18725978, 30851065, 33158149, 31447099, 31206626, 31263054, 30303537, 30676620, 31090900, 30322717, 29922827, 15095295, 12610780, 30666157, 30426508, 29659569, 29945567, 30067863, 30256826, 28125075, 29439820, 28553140, 28709830, 28503720, 28008555, 28452373, 27498913, 28082821, 26681312, 23555315, 27751358, 15488637, 15385111, 23960188, 15818573) (less)
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Likely pathogenic
(Mar 09, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004020195.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is considered likely pathogenic. This variant is strongly associated with more severe personal and family histories of cancer, typical for individuals with pathogenic … (more)
This variant is considered likely pathogenic. This variant is strongly associated with more severe personal and family histories of cancer, typical for individuals with pathogenic variants in this gene [PMID: 25085752]. (less)
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Likely pathogenic
(Jan 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV002043402.2
First in ClinVar: Jan 01, 2022 Last updated: Feb 04, 2024 |
|
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Likely pathogenic
(Dec 05, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000537618.7
First in ClinVar: Sep 24, 2016 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces arginine with glycine at codon 117 in the FHA domain of the CHEK2 protein. Computational prediction suggests that this variant may … (more)
This missense variant replaces arginine with glycine at codon 117 in the FHA domain of the CHEK2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant causes reduced kinase activity, reduced protein stability, incomplete phosphorylation of CHEK2 protein and defective DNA damage repair (PMID: 16835864, 16982735, 18725978, 22419737, 30851065, 34903604, 37449874). This variant has been reported in individuals affected with breast cancer (PMID: 12454775, 12610780, 18058223, 21244692, 22114986, 23555315, 25503501, 27553368, 27798748, 28503720, 30128536, 31263054, 33030641, 33326660, 33803639, 35264596, 36315097), colorectal cancer (PMID: 30256826), prostate cancer (PMID: 33158149), and pancreatic cancer (PMID: 29922827, 29945567). Large case-control studies have shown that this variant is associated with an increased risk of breast cancer (OR 2.26, 95% CI [1.29 to 3.95], PMID: 27595995; OR=2.936, 95%CI [1.823 to 4.73], PMID: 33471991; OR=2.83, 95% CI [2.35 to 3.41], PMID: 37449874). This variant has been identified in 32/282632 chromosomes in the general population by the Genome Aggregation Database (gnomAD). In summary, this variant has been shown to cause partial loss of CHEK2 protein function and is associated with an increased risk of breast cancer. Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
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Pathogenic
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000262374.12
First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 117 of the CHEK2 protein (p.Arg117Gly). … (more)
This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 117 of the CHEK2 protein (p.Arg117Gly). This variant is present in population databases (rs28909982, gnomAD 0.02%). This missense change has been observed in individual(s) with CHEK2-related cancers (PMID: 12454775, 12610780, 21244692, 28503720). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 128071). 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 disruptive. Experimental studies have shown that this missense change affects CHEK2 function (PMID: 16982735, 18725878, 22419737). For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(Nov 01, 2023)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV000892319.26
First in ClinVar: Mar 31, 2019 Last updated: Aug 04, 2024 |
Comment:
CHEK2: PP1:Strong, PS4, PP3, PS3:Supporting, BP1
Number of individuals with the variant: 6
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Likely pathogenic
(Mar 22, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
Center of Genomic medicine, Geneva, University Hospital of Geneva
Accession: SCV000590881.1
First in ClinVar: Apr 16, 2017 Last updated: Apr 16, 2017 |
Comment:
This CHEK2 variant was identified in a female patient diagnosed with breast cancer at 38 years old, and whose mother also have had bilateral breast … (more)
This CHEK2 variant was identified in a female patient diagnosed with breast cancer at 38 years old, and whose mother also have had bilateral breast cancer at ages 40 and 42 years old. Mutation screening in BRCA1 and BRCA2 genes gave negative results. (less)
Age: 30-39 years
Sex: female
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Pathogenic
(Oct 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Susceptibility to breast cancer
Susceptibility to prostate cancer
Affected status: unknown
Allele origin:
germline
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV001434869.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Comment:
The c.349A>G(p.Arg117Gly) variant in the CHEK2 gene (seen 31 times in gnomAD) has been observed in multiple unrelated probands and segregated in one family with … (more)
The c.349A>G(p.Arg117Gly) variant in the CHEK2 gene (seen 31 times in gnomAD) has been observed in multiple unrelated probands and segregated in one family with BRCA1/2 negative breast cancer (PMID 12454775, 12610780, 18058223, 27595995, 27553368, 27798748). Although not validated for clinical use, the in silico programs predict this variant to be damaging. Experimental studies are consistent with this variant resulting in disruption of CHEK2 function (PMID 16982735, 16835864, 22419737). Therefore, this c.349A>G (p.Arg117Gly) variant in the CHEK2 gene is classified as pathogenic. (less)
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Likely pathogenic
(Aug 01, 2020)
|
criteria provided, single submitter
Method: research
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Molecular Oncology Research Center, Barretos Cancer Hospital
Accession: SCV001438613.1
First in ClinVar: Apr 22, 2021 Last updated: Apr 22, 2021 |
Number of individuals with the variant: 1
Clinical Features:
breast cancer (present)
|
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Likely pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447125.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Sex: female
|
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Likely pathogenic
(Apr 18, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Knight Diagnostic Laboratories, Oregon Health and Sciences University
Accession: SCV001448802.1
First in ClinVar: Dec 11, 2020 Last updated: Dec 11, 2020 |
Number of individuals with the variant: 1
|
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Likely pathogenic
(Mar 25, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
CHEK2-related cancer predisposition
Affected status: yes
Allele origin:
germline
|
DASA
Accession: SCV002318957.1
First in ClinVar: Apr 02, 2022 Last updated: Apr 02, 2022 |
Comment:
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 18725978; 16982735; 22419737) - PS3_moderate. … (more)
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 18725978; 16982735; 22419737) - PS3_moderate. The c.349A>G;p.(Arg117Gly) missense change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 128071; PMID: 12454775; PMID: 12610780; PMID: 21244692; PMID: 28503720) -PS4. The variant is present at low allele frequencies population databases (rs28909982 – gnomAD 0.001132%; ABraOM 0.001281 frequency - http://abraom.ib.usp.br.) - PM2_supporting. In summary, the currently available evidence indicates that the variant is likely pathogenic (less)
Number of individuals with the variant: 1
Sex: female
Geographic origin: Brazil
|
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Likely pathogenic
(Jul 02, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV000839495.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
|
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Likely pathogenic
(Dec 09, 2022)
|
criteria provided, single submitter
Method: research
|
Familial cancer of breast
Affected status: no
Allele origin:
germline
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV002762811.2
First in ClinVar: Dec 17, 2022 Last updated: Feb 25, 2023 |
Comment:
PS3, PS4_STR
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Pathogenic
(Mar 06, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 2
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg
Accession: SCV003836493.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
Comment:
This variant has been identified by standard clinical testing.
Number of individuals with the variant: 1
|
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Likely pathogenic
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002009501.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
|
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Pathogenic
(Mar 12, 2022)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000889334.3
First in ClinVar: Sep 13, 2018 Last updated: Jan 06, 2024 |
Comment:
In the published literature, the variant has been reported in individuals with breast cancer (PMIDs: 31263054 (2019), 31206626 (2019), 31090900 (2019), 30303537 (2019), 30426508 (2018), … (more)
In the published literature, the variant has been reported in individuals with breast cancer (PMIDs: 31263054 (2019), 31206626 (2019), 31090900 (2019), 30303537 (2019), 30426508 (2018), 30128536 (2018), 28709830 (2017), 28503720 (2017), 27553368 (2016), 25503501 (2015)), prostate cancer (PMIDs: 29659569 (2018), 29439820 (2018)), and pancreatic cancer (PMIDs: 29945567 (2018), 29922827 (2018)). In addition, families show evidence of co-segregation with breast cancer (PMID: 12610780 (2003)). Functional studies in the published literature report this variant causes loss of CHEK2 activity (PMIDs: 30851065 (2019), 22419737 (2012), 18725978 (2008), 16982735 (2006), 16835864 (2006)). The frequency of this variant in the general population, 0.00019 (24/128958 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. (less)
|
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Likely pathogenic
(Feb 06, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004242520.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
|
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Likely pathogenic
(May 15, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
CHEK2-related cancer predisposition
Affected status: unknown
Allele origin:
unknown
|
Illumina Laboratory Services, Illumina
Accession: SCV004801674.1
First in ClinVar: Mar 23, 2024 Last updated: Mar 23, 2024 |
Comment:
The CHEK2 c.349A>G p.(Arg117Gly), also referred to c.478A>G (Arg160Gly), missense variant has been identified in individuals with a phenotype consistent with CHEK2-related cancer susceptibility. In … (more)
The CHEK2 c.349A>G p.(Arg117Gly), also referred to c.478A>G (Arg160Gly), missense variant has been identified in individuals with a phenotype consistent with CHEK2-related cancer susceptibility. In two individuals, other pathogenic BRCA2 and CHEK2 variants were also identified (Sodha et al. 2002; Schutte et al. 2003; Le Calvez-Kelm et al. 2011; Southey et al. 2016; Susswein et al. 2016). In a large case-control study, Southey et al. (2016) showed that the p.(Arg117Gly) variant was significantly associated with breast cancer in European women (odds ratio of 2.26). In this study, odd ratios were not statistically significant for prostate cancer or ovarian cancer. The variant segregated with breast cancer in one family whereas in two families incomplete segregation was observed whereby two affected individuals did not carry the variant (Schutte et al. 2003). The highest frequency of this allele in the Genome Aggregation Database is 0.000186 in the European (non-Finnish) population (version 2.1.1). Functional studies in cells lines demonstrated reduced protein expression and stability, and impaired phosphorylation and kinase activity of the variant protein when compared to wildtype protein. However, the variant protein dimerized efficiently to wildtype CHEK2 (Sodha et al. 2006; Wu et al. 2006; Chrisanthar et al. 2008). Multiple lines of computational evidence suggest the variant may impact the gene or gene product. Based on the available evidence, the c.349A>G p.(Arg117Gly) variant is classified as likely pathogenic for CHEK2-related breast cancer susceptibility. (less)
|
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Likely pathogenic
(Sep 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000183898.9
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.R117G variant (also known as c.349A>G), located in coding exon 2 of the CHEK2 gene, results from an A to G substitution at nucleotide … (more)
The p.R117G variant (also known as c.349A>G), located in coding exon 2 of the CHEK2 gene, results from an A to G substitution at nucleotide position 349. The arginine at codon 117 is replaced by glycine, an amino acid with dissimilar properties. This alteration has been identified in many cancer cases including familial breast/ovarian, pancreatic and colorectal and prostate cancer cohorts (Sodha N et al. Br. J. Cancer. 2002 Dec;87:1445-8; Kleibl Z et al. Breast Cancer Res. Treat. 2008 Nov;112:159-64; Desrichard A et al. Breast Cancer Res. 2011 Nov;13:R119; Le Calvez-Kelm F et al. Breast Cancer Res. 2011 Jan;13:R6; Moran O et al. Breast Cancer Res. Treat. 2017 Jan;161:135-142; Pinto P et al. Breast Cancer Res. Treat. 2016 Sep;159:245-56; Schutte M et al. Am. J. Hum. Genet. 2003 Apr;72:1023-8). This variant has also been reported to be a possible European founder variant leading to a significant increase in prostate cancer risk (Brandão A et al. Cancers (Basel). 2020 Nov;12(11)). Multiple functional studies have found that this variant is abnormal with respect to protein stability and kinase activity (Sodha N et al. Cancer Res. 2006 Sep;66:8966-70; Chrisanthar R et al. PLoS One. 2008 Aug;3:e3062; Roeb W et al. Hum. Mol. Genet. 2012 Jun;21:2738-44; Wu X et al. Hum. Mutat. 2006 Aug;27:742-7; Delimitsou A et al. Hum. Mutat. 2019 May;40(5):631-648; Boonen RACM et al. Cancer Res, 2022 Feb;82:615-631). This alteration was also more frequent in breast cancer cases than controls in a study from the Breast Cancer Association Consortium (BCAC) (Southey MC et al. J. Med. Genet., 2016 12;53:800-811). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
|
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Pathogenic
(Nov 24, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005197506.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
|
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000691836.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
|
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001550444.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The CHEK2 p.Arg117Gly variant was identified in 55 of 88752 proband chromosomes (frequency: 0.0006) from individuals or families with hereditary breast and ovarian cancer (Desrichard … (more)
The CHEK2 p.Arg117Gly variant was identified in 55 of 88752 proband chromosomes (frequency: 0.0006) from individuals or families with hereditary breast and ovarian cancer (Desrichard 2011, Kleibl 2008, Moran 2017, Pinto 2016, Schutte 2003, Sodha 2002, Southey 2016, Wu 2006). The variant was also identified in dbSNP (ID: rs28909982) as “With Pathogenic allele”, ClinVar (as pathogenic by GeneDx and Mayo Clinic; and as likely pathogenic by Ambry Genetics, Invitae, Color Genomics, University Hospital of Geneva, and Counsyl), MutDB, and Zhejiang Colon Cancer Database (4x). The variant was not identified in the Cosmic database. The variant was identified in control databases in 31 of 276970 chromosomes at a frequency of 0.0001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 2 of 24030 chromosomes (freq: 0.00008), Other in 1 of 6464 chromosomes (freq: 0.0002), Latino in 4 of 34418 chromosomes (freq: 0.0001), European in 22 of 126468 chromosomes (freq: 0.0002), Finnish in 2 of 25792 chromosomes (freq: 0.00008), while the variant was not observed in the Ashkenazi Jewish, East Asian, or South Asian populations. The p.Arg117Gly variant has been extensively studied in the literature. In vitro studies have demonstrated that the Arg117Gly variant has strongly reduced kinase activity (Chrisanthar 2008). Multiple studies found that following DNA damage with ionizing radiation, the variant protein demonstrated greatly reduced CHEK2 kinase activity (Wu 2006, Roeb 2012, Le Calvez-Kelm 2011). In addition, studies have shown that the protein encoded by this allele is phosphorylated by ATM in response to DNA damage, shows slightly to markedly reduced autophosphorylation, probably fails to oligomerize, and has severely compromised kinase activity. Sodha (2006) also concluded through bioinformatic analysis that the variant is likely to be deleterious and functional studies showed that the variant protein is less stable than the wild type protein. The p.Arg117Gly residue is conserved across mammals and other organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
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Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001906416.1 First in ClinVar: Sep 23, 2021 Last updated: Sep 23, 2021 |
|
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Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001963773.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
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Likely pathogenic
(Oct 09, 2023)
|
no assertion criteria provided
Method: clinical testing
|
Li-Fraumeni syndrome 2
Affected status: yes
Allele origin:
germline
|
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas
Accession: SCV004041663.1
First in ClinVar: Oct 14, 2023 Last updated: Oct 14, 2023 |
|
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Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799322.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
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Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808713.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
|
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Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001742938.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
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Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001958164.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
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not provided
(-)
|
no classification provided
Method: phenotyping only
|
Not Provided
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect, ClinGen
Accession: SCV000784695.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical … (more)
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Myopia (present) , Increased susceptibility to fractures (present) , Abnormality of the ureter (present) , Renal neoplasm (present) , Neoplasm of ovary (present)
Age: 20-29 years
Sex: female
Testing laboratory: Myriad Genetic Laboratories, Inc.,Myriad Genetic Laboratories, Inc.
Date variant was reported to submitter: 2014-10-10
Testing laboratory interpretation: Uncertain significance
|
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not provided
(-)
|
no classification provided
Method: phenotyping only
|
CHEK2-related cancer predisposition
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect - Invitae Patient Insights Network
Accession: SCV001749392.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
Comment:
Variant interpreted as Likely pathogenic and reported on 03-13-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided … (more)
Variant interpreted as Likely pathogenic and reported on 03-13-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Clinical Features:
Family history of cancer (present)
Indication for testing: Presymptomatic, Family Testing
Age: 40-49 years
Sex: female
Testing laboratory: Invitae
Date variant was reported to submitter: 2018-03-13
Testing laboratory interpretation: Likely pathogenic
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
ENIGMA CHEK2gether Project: A Comprehensive Study Identifies Functionally Impaired CHEK2 Germline Missense Variants Associated with Increased Breast Cancer Risk. | Stolarova L | Clinical cancer research : an official journal of the American Association for Cancer Research | 2023 | PMID: 37449874 |
Somatic inactivation of breast cancer predisposition genes in tumors associated with pathogenic germline variants. | Lim BWX | Journal of the National Cancer Institute | 2023 | PMID: 36315097 |
Detection of germline variants in Brazilian breast cancer patients using multigene panel testing. | Guindalini RSC | Scientific reports | 2022 | PMID: 35264596 |
Functional Analysis Identifies Damaging CHEK2 Missense Variants Associated with Increased Cancer Risk. | Boonen RACM | Cancer research | 2022 | PMID: 34903604 |
Population-Based Estimates of the Age-Specific Cumulative Risk of Breast Cancer for Pathogenic Variants in CHEK2: Findings from the Australian Breast Cancer Family Registry. | Nguyen-Dumont T | Cancers | 2021 | PMID: 33803639 |
Whole-exome sequencing of non-BRCA1/BRCA2 mutation carrier cases at high-risk for hereditary breast/ovarian cancer. | Felicio PS | Human mutation | 2021 | PMID: 33326660 |
Bilateral Disease Common Among Slovenian CHEK2-Positive Breast Cancer Patients. | Nizic-Kos T | Annals of surgical oncology | 2021 | PMID: 33030641 |
Multigene panel testing for hereditary breast and ovarian cancer in the province of Ontario. | Lerner-Ellis J | Journal of cancer research and clinical oncology | 2021 | PMID: 32885271 |
The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor. | Brandão A | Cancers | 2020 | PMID: 33158149 |
Comprehensive analysis and ACMG-based classification of CHEK2 variants in hereditary cancer patients. | Vargas-Parra G | Human mutation | 2020 | PMID: 32906215 |
Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network. | eMERGE Consortium. Electronic address: agibbs@bcm.edu | American journal of human genetics | 2019 | PMID: 31447099 |
Frequency of Pathogenic Germline Variants in CDH1, BRCA2, CHEK2, PALB2, BRCA1, and TP53 in Sporadic Lobular Breast Cancer. | Petridis C | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2019 | PMID: 31263054 |
Pathogenic and likely pathogenic variants in PALB2, CHEK2, and other known breast cancer susceptibility genes among 1054 BRCA-negative Hispanics with breast cancer. | Weitzel JN | Cancer | 2019 | PMID: 31206626 |
Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers. | Nones K | Annals of oncology : official journal of the European Society for Medical Oncology | 2019 | PMID: 31090900 |
Identification of deleterious germline CHEK2 mutations and their association with breast and ovarian cancer. | Kleiblova P | International journal of cancer | 2019 | PMID: 31050813 |
Functional characterization of CHEK2 variants in a Saccharomyces cerevisiae system. | Delimitsou A | Human mutation | 2019 | PMID: 30851065 |
Association of Inherited Pathogenic Variants in Checkpoint Kinase 2 (CHEK2) With Susceptibility to Testicular Germ Cell Tumors. | AlDubayan SH | JAMA oncology | 2019 | PMID: 30676620 |
Genetic analysis of subsequent second primary malignant neoplasms in long-term pancreatic cancer survivors suggests new potential hereditary genetic alterations. | Lovecek M | Cancer management and research | 2019 | PMID: 30666157 |
The identification of pathogenic variants in BRCA1/2 negative, high risk, hereditary breast and/or ovarian cancer patients: High frequency of FANCM pathogenic variants. | Schubert S | International journal of cancer | 2019 | PMID: 30426508 |
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 | International journal of cancer | 2019 | PMID: 30303537 |
Association of Breast and Ovarian Cancers With Predisposition Genes Identified by Large-Scale Sequencing. | Lu HM | JAMA oncology | 2019 | PMID: 30128536 |
Germline pathogenic variants identified in women with ovarian tumors. | Carter NJ | Gynecologic oncology | 2018 | PMID: 30322717 |
Novel genetic mutations detected by multigene panel are associated with hereditary colorectal cancer predisposition. | Martin-Morales L | PloS one | 2018 | PMID: 30256826 |
Prospective study of germline genetic testing in incident cases of pancreatic adenocarcinoma. | Brand R | Cancer | 2018 | PMID: 30067863 |
Pancreatic cancer as a sentinel for hereditary cancer predisposition. | Young EL | BMC cancer | 2018 | PMID: 29945567 |
Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer. | Hu C | JAMA | 2018 | PMID: 29922827 |
Targeted next generation sequencing identifies functionally deleterious germline mutations in novel genes in early-onset/familial prostate cancer. | Paulo P | PLoS genetics | 2018 | PMID: 29659569 |
Germline DNA-repair Gene Mutations and Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Receiving First-line Abiraterone and Enzalutamide. | Antonarakis ES | European urology | 2018 | PMID: 29439820 |
Pathologic findings in breast, fallopian tube, and ovary specimens in non-BRCA hereditary breast and/or ovarian cancer syndromes: a study of 18 patients with deleterious germline mutations in RAD51C, BARD1, BRIP1, PALB2, MUTYH, or CHEK2. | Schoolmeester JK | Human pathology | 2017 | PMID: 28709830 |
Contribution of germline mutations in cancer predisposition genes to tumor etiology in young women diagnosed with invasive breast cancer. | Rummel SK | Breast cancer research and treatment | 2017 | PMID: 28503720 |
Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study. | Ghazani AA | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 28125075 |
Male breast cancer in a multi-gene panel testing cohort: insights and unexpected results. | Pritzlaff M | Breast cancer research and treatment | 2017 | PMID: 28008555 |
Revisiting breast cancer patients who previously tested negative for BRCA mutations using a 12-gene panel. | Moran O | Breast cancer research and treatment | 2017 | PMID: 27798748 |
Efficiency of olaparib in colorectal cancer patients with an alteration of the homologous repair protein. | Ghiringhelli F | World journal of gastroenterology | 2016 | PMID: 28082821 |
Breast cancer risk is similar for CHEK2 founder and non-founder mutation carriers. | Leedom TP | Cancer genetics | 2016 | PMID: 27751358 |
PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS. | Southey MC | Journal of medical genetics | 2016 | PMID: 27595995 |
Implementation of next-generation sequencing for molecular diagnosis of hereditary breast and ovarian cancer highlights its genetic heterogeneity. | Pinto P | Breast cancer research and treatment | 2016 | PMID: 27553368 |
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. | Susswein LR | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26681312 |
Prevalence of mutations in a panel of breast cancer susceptibility genes in BRCA1/2-negative patients with early-onset breast cancer. | Maxwell KN | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25503501 |
Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes. | Pruss D | Breast cancer research and treatment | 2014 | PMID: 25085752 |
Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients. | LaDuca H | Genetics in medicine : official journal of the American College of Medical Genetics | 2014 | PMID: 24763289 |
Genome-wide testing of putative functional exonic variants in relationship with breast and prostate cancer risk in a multiethnic population. | Haiman CA | PLoS genetics | 2013 | PMID: 23555315 |
Response to DNA damage of CHEK2 missense mutations in familial breast cancer. | Roeb W | Human molecular genetics | 2012 | PMID: 22419737 |
CHEK2 contribution to hereditary breast cancer in non-BRCA families. | Desrichard A | Breast cancer research : BCR | 2011 | PMID: 22114986 |
Two new CHEK2 germ-line variants detected in breast cancer/sarcoma families negative for BRCA1, BRCA2, and TP53 gene mutations. | Manoukian S | Breast cancer research and treatment | 2011 | PMID: 21562711 |
Rare, evolutionarily unlikely missense substitutions in CHEK2 contribute to breast cancer susceptibility: results from a breast cancer family registry case-control mutation-screening study. | Le Calvez-Kelm F | Breast cancer research : BCR | 2011 | PMID: 21244692 |
CHEK2 mutations affecting kinase activity together with mutations in TP53 indicate a functional pathway associated with resistance to epirubicin in primary breast cancer. | Chrisanthar R | PloS one | 2008 | PMID: 18725978 |
Peptide-conjugated antisense therapy takes a skip ahead. | Wells DJ | Molecular therapy : the journal of the American Society of Gene Therapy | 2008 | PMID: 18725878 |
Analysis of CHEK2 FHA domain in Czech patients with sporadic breast cancer revealed distinct rare genetic alterations. | Kleibl Z | Breast cancer research and treatment | 2008 | PMID: 18058223 |
Rare germ line CHEK2 variants identified in breast cancer families encode proteins that show impaired activation. | Sodha N | Cancer research | 2006 | PMID: 16982735 |
Characterization of CHEK2 mutations in prostate cancer. | Wu X | Human mutation | 2006 | PMID: 16835864 |
Limited relevance of the CHEK2 gene in hereditary breast cancer. | Dufault MR | International journal of cancer | 2004 | PMID: 15095295 |
Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility. | Schutte M | American journal of human genetics | 2003 | PMID: 12610780 |
CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours. | Sodha N | British journal of cancer | 2002 | PMID: 12454775 |
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Text-mined citations for rs28909982 ...
HelpRecord last updated Aug 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.