Submissions for variant NM_007194.4(CHEK2):c.1542+7G>A

dbSNP: rs4035547

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000582133	SCV000689666	likely benign	Hereditary cancer-predisposing syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV001442837	SCV001645792	likely benign	Familial cancer of breast	2023-10-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001797754	SCV002041723	uncertain significance	not specified	2021-11-24	criteria provided, single submitter	clinical testing	Variant summary: CHEK2 c.1542+7G>A alters a non-conserved nucleotide located close to a canonical splice site in the last intron and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 233372 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1542+7G>A (also known as c.1455+7G>A) have been observed in individuals affected with breast cancer without evidence for causality (example: Mucaki_2016). To our knowledge no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.