Submissions for variant NM_007194.4(CHEK2):c.79C>T (p.Gln27Ter)

dbSNP: rs376736188

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000635876	SCV000757301	pathogenic	Familial cancer of breast	2021-12-17	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 530172). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln27*) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400).
Ambry Genetics	RCV001027035	SCV001189533	pathogenic	Hereditary cancer-predisposing syndrome	2019-06-10	criteria provided, single submitter	clinical testing	The p.Q27* pathogenic mutation (also known as c.79C>T), located in coding exon 1 of the CHEK2 gene, results from a C to T substitution at nucleotide position 79. This changes the amino acid from a glutamine to a stop codon within coding exon 1. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc.	RCV000635876	SCV004043312	pathogenic	Familial cancer of breast	2023-06-22	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University School of Medicine.	RCV001543607	SCV001754535	pathogenic	Colorectal cancer	2021-07-16	no assertion criteria provided	research	The Gln27* variant in CHEK2 has been reported in 1 Chinese family with autosomal dominant predisposition in familial colorectal cancer (CRC). Additionally, in vitro functional studies indicate that the CHEK2 knockout cells showed defective cell cycle arrest and apoptosis and reduced p53 phosphorylation upon DNA damage. A second variant in CHEK2 was found in 126 sporadic CRCs. In summary, the Gln27* variant in CHEK2 meets our criteria to be classified as likely pathogenic based upon segregation studies, absence from controls, and functional evidence.