ClinVar Genomic variation as it relates to human health
NM_007194.4(CHEK2):c.917G>T (p.Gly306Val)
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.917G>T (p.Gly306Val)
Variation ID: 823069 Accession: VCV000823069.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 22q12.1 22: 28699929 (GRCh38) [ NCBI UCSC ] 22: 29095917 (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 Mar 16, 2020 May 1, 2024 Oct 16, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007194.4:c.917G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009125.1:p.Gly306Val missense NM_001005735.2:c.1046G>T NP_001005735.1:p.Gly349Val missense NM_001257387.2:c.254G>T NP_001244316.1:p.Gly85Val missense NM_001349956.2:c.716G>T NP_001336885.1:p.Gly239Val missense NM_145862.2:c.917G>T NP_665861.1:p.Gly306Val missense NC_000022.11:g.28699929C>A NC_000022.10:g.29095917C>A NG_008150.2:g.46938G>T LRG_302:g.46938G>T LRG_302t1:c.917G>T LRG_302p1:p.Gly306Val - Protein change
- G239V, G85V, G306V, G349V
- Other names
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- Canonical SPDI
- NC_000022.11:28699928:C:A
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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
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Sep 14, 2022 | RCV001018963.8 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Oct 16, 2023 | RCV001873314.5 |
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
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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
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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
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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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Uncertain significance
(Nov 01, 2018)
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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: SCV001358947.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
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Uncertain significance
(Jun 12, 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: SCV002537655.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The CHEK2 c.917G>T (p.G306V) variant has been reported in individuals with breast cancer (PMID: 31465090, 30306255, 30287823). It was not observed in the large and … (more)
The CHEK2 c.917G>T (p.G306V) variant has been reported in individuals with breast cancer (PMID: 31465090, 30306255, 30287823). It was not observed in the large and broad cohorts of the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). The variant has been reported in ClinVar (Variation ID: 823069). In silico tools suggest the impact of the variant on protein function is inconclusive, though these predictions have not been confirmed by functional studies. The evidence is insufficient to meet ACMG/AMP criteria for classifying the variant as benign or pathogenic. Thus, the clinical significance of this variant is currently uncertain. (less)
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Uncertain significance
(Oct 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004100717.1
First in ClinVar: Nov 04, 2023 Last updated: Nov 04, 2023 |
Comment:
Criteria applied: PS3_supp, PM5,PM2_SUP,PP3
Clinical Features:
Breast carcinoma (present)
Sex: female
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Uncertain significance
(Dec 30, 2022)
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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: SCV002159835.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
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 … (more)
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 823069). This missense change has been observed in individual(s) with breast cancer (PMID: 30287823, 30306255, 31465090). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 306 of the CHEK2 protein (p.Gly306Val). (less)
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Uncertain significance
(Sep 14, 2022)
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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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Ambry Genetics
Accession: SCV001180262.4
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
The p.G306V variant (also known as c.917G>T), located in coding exon 8 of the CHEK2 gene, results from a G to T substitution at nucleotide … (more)
The p.G306V variant (also known as c.917G>T), located in coding exon 8 of the CHEK2 gene, results from a G to T substitution at nucleotide position 917. The glycine at codon 306 is replaced by valine, an amino acid with dissimilar properties. This alteration has been identified in a Spanish breast cancer patient who was diagnosed at age 35 (Bonache S et al. J. Cancer Res. Clin. Oncol., 2018 Dec;144:2495-2513) and in 1/7051 female breast cancer cases and 2/11241 controls from Japan (Momozawa Y et al. Nat Commun, 2018 10;9:4083). It has also been reported in an individual with metastatic breast cancer (Stuttgen K et al. JAMA Oncol, 2019 Oct;5:1506-1508). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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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 |
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Pathogenic Germline Variants in Patients With Metastatic Breast Cancer. | Stuttgen K | JAMA oncology | 2019 | PMID: 31465090 |
Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings. | Bonache S | Journal of cancer research and clinical oncology | 2018 | PMID: 30306255 |
Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. | Momozawa Y | Nature communications | 2018 | PMID: 30287823 |
Text-mined citations for rs587780192 ...
HelpRecord last updated May 08, 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.