Submissions for variant NM_007194.4(CHEK2):c.612G>T (p.Leu204=)

dbSNP: rs752876192

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000579370	SCV000680807	uncertain significance	not provided	2017-09-29	criteria provided, single submitter	clinical testing	This variant is denoted CHEK2 c.612G>T at the DNA level. Although this variant is silent at the coding level, preserving a Leucine at codon 204, it is predicted to increase the strength of a downstream splice acceptor site and to potentially cause abnormal splicing. In the absence of RNA or functional studies, however, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. This variant was not observed in large population cohorts (Lek 2016). The nucleotide which is altered, a guanine (G) at base 612, is conserved in mammals. Based on currently available information, it is unclear whether CHEK2 c.612G>T is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000780179	SCV000917229	likely benign	not specified	2019-08-28	criteria provided, single submitter	clinical testing
Invitae	RCV001443690	SCV001646674	likely benign	Familial cancer of breast	2023-07-12	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798901	SCV002043410	likely benign	Breast and/or ovarian cancer	2019-07-29	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002257848	SCV002537627	uncertain significance	Hereditary cancer-predisposing syndrome	2022-02-10	criteria provided, single submitter	curation
Ambry Genetics	RCV002257848	SCV002654426	likely benign	Hereditary cancer-predisposing syndrome	2019-03-07	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.