Submissions for variant NM_007194.4(CHEK2):c.1542+11T>A

gnomAD frequency: 0.01583  dbSNP: rs17881716

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129000	SCV000172895	benign	Hereditary cancer-predisposing syndrome	2012-08-14	criteria provided, single submitter	clinical testing	General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Illumina Laboratory Services, Illumina	RCV000304239	SCV000437708	likely benign	CHEK2-Related Cancer Susceptibility	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Counsyl	RCV000410734	SCV000488265	benign	Familial cancer of breast	2016-02-16	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000129000	SCV000684607	benign	Hereditary cancer-predisposing syndrome	2015-04-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000679677	SCV000806875	benign	not specified	2017-03-20	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985701	SCV001134161	benign	not provided	2019-03-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000985701	SCV001834707	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Invitae	RCV000410734	SCV002402494	benign	Familial cancer of breast	2024-02-01	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225422	SCV002505152	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000679677	SCV002761094	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000410734	SCV004017047	benign	Familial cancer of breast	2023-07-07	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357010	SCV001552333	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The CHEK2 c.1542+11T>A variant was not identified in the literature nor was it identified in the Cosmic, MutDB or Zhejiang Colon Cancer databases. The variant was identified in the following databases: dbSNP (ID: rs17881716) as "With Likely benign allele", in ClinVar (classified as benign 2x, likely benign 2x), and Clinvitae (classified as benign 2x, likely benign 2x). The variant was identified in control databases in 1364 of 259656 chromosomes (43 homozygous) at a frequency of 0.005 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations at a frequency greater than 1%: African in 1294 of 22484 chromosomes (freq: 0.06). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000679677	SCV001809620	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000679677	SCV001905749	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000679677	SCV001953987	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000985701	SCV002036595	likely benign	not provided		no assertion criteria provided	clinical testing