Submissions for variant NM_000059.4(BRCA2):c.9257-8C>T

dbSNP: rs11571819

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001088131	SCV000253058	likely benign	Hereditary breast ovarian cancer syndrome	2025-01-23	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759690	SCV000889183	likely benign	not provided	2018-03-23	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000773110	SCV000906591	likely benign	Hereditary cancer-predisposing syndrome	2016-05-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000780036	SCV000917050	benign	not specified	2022-11-24	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.9257-8C>T alters a non-conserved nucleotide located close to a canonical splice site 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 allele was found at a frequency of 1.6e-05 in 244366 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.9257-8C>T has been reported in the literature as a VUS in individuals affected with Breast and/or Ovarian Cancer (example, Hansen_2009, Lu_2012). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. At-least two co-occurrences with other pathogenic variant(s) have been observed at our laboratory (CHEK2 c.1100delC, p.Thr367MetfsX15; RAD51C c.397C>T, p.Gln133X), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Mendelics	RCV000077038	SCV001139252	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2019-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000759690	SCV001758315	benign	not provided	2015-09-12	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000780036	SCV002551846	likely benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492429	SCV004240376	likely benign	Breast and/or ovarian cancer	2023-05-01	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000077038	SCV004822646	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-06-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000773110	SCV004848936	uncertain significance	Hereditary cancer-predisposing syndrome	2015-12-29	criteria provided, single submitter	clinical testing	The c.9257-8C>T intronic alteration consists of a C to T substitution 8 nucleotides before coding exon 24 in the BRCA2 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Sharing Clinical Reports Project (SCRP)	RCV000077038	SCV000108835	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2012-02-10	no assertion criteria provided	clinical testing