NM_007194.4(CHEK2):c.89_90insAG (p.Ser31fs) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 2, 2022
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:: RCV002266437.1

Allele description [Variation Report for NM_007194.4(CHEK2):c.89_90insAG (p.Ser31fs)]

NM_007194.4(CHEK2):c.89_90insAG (p.Ser31fs)

Gene:

CHEK2:checkpoint kinase 2 [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

22q12.1

Genomic location:

Preferred name:

NM_007194.4(CHEK2):c.89_90insAG (p.Ser31fs)

HGVS:

NC_000022.11:g.28734633_28734634insTC
NG_008150.2:g.12234_12235insAG
NM_001005735.2:c.89_90insAG
NM_001257387.2:c.-689_-688insAG
NM_001349956.2:c.89_90insAG
NM_007194.4:c.89_90insAGMANE SELECT
NM_145862.2:c.89_90insAG
NP_001005735.1:p.Ser31fs
NP_001336885.1:p.Ser31fs
NP_009125.1:p.Ser31fs
NP_665861.1:p.Ser31fs
LRG_302t1:c.89_90insAG
LRG_302:g.12234_12235insAG
LRG_302p1:p.Ser31fs
NC_000022.10:g.29130621_29130622insTC
NM_007194.3:c.89_90insAG

Protein change:

S31fs

Links:

dbSNP: rs2146152668

NCBI 1000 Genomes Browser:

rs2146152668

Molecular consequence:

NM_001257387.2:c.-689_-688insAG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001005735.2:c.89_90insAG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001349956.2:c.89_90insAG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_007194.4:c.89_90insAG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_145862.2:c.89_90insAG - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002548436	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (May 2, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002548436

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(May 2, 2022)

germline

clinical testing

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002548436.1

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

Description

Variant summary: CHEK2 c.89_90insAG (p.Ser31AlafsX31) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 249506 control chromosomes (gnomAD). To our knowledge, no occurrence of c.89_90insAG in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	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: Jul 15, 2024

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