Submissions for variant NM_007194.4(CHEK2):c.*7T>C

gnomAD frequency: 0.00009  dbSNP: rs121908710

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000160461	SCV000211026	benign	not specified	2014-09-08	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000206507	SCV000259982	uncertain significance	Familial cancer of breast	2015-08-16	criteria provided, single submitter	clinical testing	This sequence change falls in the 3'UTR of the CHEK2 gene. It does not change the encoded amino acid sequence of the CHEK2 protein. This variant is present in population databases (rs121908710, 0.02%) and has been reported in the literature. ClinVar contains an entry for this variant (RCV000160461, RCV000119290 ). In summary, this is rare change that is not expected to impact CHEK2 protein. However the evidence is insufficient at this time to prove that conclusively. It has been classified as a Variant of Uncertain Significance.
Counsyl	RCV000206507	SCV000488398	uncertain significance	Familial cancer of breast	2016-03-18	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000160461	SCV000594111	uncertain significance	not specified	2016-10-11	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000584174	SCV000689619	likely benign	Hereditary cancer-predisposing syndrome	2015-09-08	criteria provided, single submitter	clinical testing
Mendelics	RCV000206507	SCV001141344	likely benign	Familial cancer of breast	2019-05-28	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000160461	SCV004243011	likely benign	not specified	2024-02-06	criteria provided, single submitter	clinical testing
Institute. of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague	RCV000119290	SCV000154114	not provided	not provided		no assertion provided	not provided
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355148	SCV001549942	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The CHEK2 c.*7T>C variant was not identified in the literature. The variant was identified in dbSNP (ID: rs121908710) as "With other allele", ClinVar (classified as benign by GeneDx; as likely being by Color; as uncertain significance by three submitters). The variant was identified in control databases in 40 of 260056 chromosomes at a frequency of 0.0002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 7 of 121970 chromosomes (freq: 0.00006), Ashkenazi Jewish in 33 of 9956 chromosomes (freq: 0.003), while the variant was not observed in the African, Other, Latino, East Asian, Finnish, and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.