VCV001077093.23 - ClinVar

NM_007194.4(CHEK2):c.908+1540_1095+330del

Germline

Classification

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.

(4)

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.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_007194.4(CHEK2):c.908+1540_1095+330del

Variation ID: 1077093 Accession: VCV001077093.23

Type and length

Deletion, 5,395 bp

Location

Cytogenetic: 22q12.1 22: 28696571-28701965 (GRCh38) [ NCBI UCSC ] 22: 29092559-29097953 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	May 14, 2021	Aug 25, 2024	Mar 28, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_007194.4:c.908+1540_1095+330del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice acceptor splice donor
NM_007194.4:c.909-2028_1095+330del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice acceptor splice donor
NM_001005735.2:c.1037+1540_1224+330del		splice acceptor splice donor
NM_001257387.2:c.245+1540_432+330del		splice acceptor splice donor
NM_001349956.2:c.707+1540_894+330del		splice acceptor splice donor
NM_145862.2:c.908+1540_1009-698del		splice acceptor splice donor
NC_000022.11:g.28696573_28701967del
NC_000022.10:g.29092561_29097955del
NG_008150.2:g.44902_50296del
LRG_302:g.44902_50296del
LRG_302t1:c.908+1540_1095+330del

... more HGVS ... less HGVS

Protein change

Other names

5.4-KB DEL

Canonical SPDI

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

dbVar: nssv1415003 dbVar: nsv513775 OMIM: 604373.0012 VarSome

Comment on variant

OMIM allelic variant 604373.0012 cites two papers reporting the deletion of exons 9 and 10. Walsh et al., 2006 (PubMed 16551709) reported the location as 27416941-27422508 whereas the the paper by Cybulski et al., 2006 (PubMed 17085682) reported the location as 27417113-27422508. Because the latter paper also reported the sequence across the breakpoint, NCBI staff determined that the authors were reporting locations relative to NC_000022.8. NCBI staff generated an HGVS expression for the deletion, consistent with the sequence in Figure 1.

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
Gene	OMIM	HI score Help 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.
CHEK2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	4053	4109

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.
Carcinoma of pancreas	Pathogenic (1)	no assertion criteria provided	Mar 4, 2021	RCV001391211.1
Familial cancer of breast	Pathogenic (1)	no assertion criteria provided	Aug 26, 2022	RCV003155976.1
TUMOR PREDISPOSITION SYNDROME 4, BREAST/PROSTATE	Pathogenic (1)	no assertion criteria provided	Nov 1, 2006	RCV003441149.1
not provided	Pathogenic (1)	criteria provided, single submitter	Mar 28, 2024	RCV004697132.1

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.
Pathogenic (Mar 28, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics Laboratory, Skane University Hospital Lund Accession: SCV005197196.1 First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024
Pathogenic (Mar 04, 2021)	no assertion criteria provided Method: case-control	Carcinoma of pancreas Affected status: yes Allele origin: germline	CZECANCA consortium Accession: SCV001593127.1 First in ClinVar: May 14, 2021 Last updated: May 14, 2021	Number of individuals with the variant: 1 Ethnicity/Population group: Slavic Geographic origin: Czech Republic
Pathogenic (Aug 26, 2022)	no assertion criteria provided Method: clinical testing	Familial cancer of breast Affected status: yes Allele origin: germline	BRCAlab, Lund University Accession: SCV002588972.1 First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023
Pathogenic (Nov 01, 2006)	no assertion criteria provided Method: literature only	TUMOR PREDISPOSITION SYNDROME 4, BREAST/PROSTATE Affected status: not provided Allele origin: germline	OMIM Accession: SCV000026131.2 First in ClinVar: Apr 04, 2013 Last updated: Nov 24, 2017	Publications: PubMed (2) PubMed: 16551709‚ 17085682 Comment on evidence: Walsh et al. (2006) identified a 5.6-kb deletion encompassing exons 9 and 10 of the CHEK2 gene in affected members of probands of 2 families … (more) Walsh et al. (2006) identified a 5.6-kb deletion encompassing exons 9 and 10 of the CHEK2 gene in affected members of probands of 2 families with breast cancer (see TPDS4, 609265). Both families were of Czechoslovakian ancestry. The deletion was identified in 8 (1.3%) of 631 additional Czech patients with breast cancer and none of 367 healthy controls. Cybulski et al. (2006) identified a CHEK2 5.4-kb deletion in 15 (0.8%) of 1,864 Polish men with prostate cancer, in 4 (1.6%) of 249 Polish men with familial prostate cancer, and in 24 (0.4%) of 5,496 healthy controls. Data analysis yielded an odds ratio of 3.7 for familial prostate cancer in carriers of the deletion. The authors determined that it is a founder mutation. Cybulski et al. (2006) estimated the length of the deletion to be 5.4 kb rather than 5.6 kb as reported by Walsh et al. (2006). (less)

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

Title	Author	Journal	Year	Link
A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer.	Cybulski C	Journal of medical genetics	2006	PMID: 17085682
Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer.	Walsh T	JAMA	2006	PMID: 16551709

Text-mined citations for this variant ...

Record last updated Sep 08, 2024

ClinVar Genomic variation as it relates to human health

NM_007194.4(CHEK2):c.908+1540_1095+330del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...