Submissions for variant NM_000059.4(BRCA2):c.1166C>T (p.Pro389Leu)

dbSNP: rs397507263

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001085676	SCV000252995	likely benign	Hereditary breast ovarian cancer syndrome	2024-01-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000589187	SCV000516030	likely benign	not provided	2019-03-12	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27616075)
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000439294	SCV000600470	uncertain significance	not specified	2016-08-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000571104	SCV000661187	likely benign	Hereditary cancer-predisposing syndrome	2019-03-08	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000439294	SCV000694514	uncertain significance	not specified	2024-06-12	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.1166C>T (p.Pro389Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 250046 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in BRCA2 causing Hereditary Breast And Ovarian Cancer Syndrome (4e-05 vs 0.00075), allowing no conclusion about variant significance. c.1166C>T has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome without evidence for causality. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 27616075, 35918668, 35534704). ClinVar contains an entry for this variant (Variation ID: 37727). Based on the evidence outlined above, the variant was classified as uncertain significance.
Color Diagnostics, LLC DBA Color Health	RCV000571104	SCV000903277	benign	Hereditary cancer-predisposing syndrome	2016-09-14	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV001085676	SCV002026064	likely benign	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000571104	SCV002533212	uncertain significance	Hereditary cancer-predisposing syndrome	2021-08-10	criteria provided, single submitter	curation
University of Washington Department of Laboratory Medicine, University of Washington	RCV000571104	SCV003849888	likely benign	Hereditary cancer-predisposing syndrome	2023-03-23	criteria provided, single submitter	curation	Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Sharing Clinical Reports Project (SCRP)	RCV000031308	SCV000053913	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2012-05-31	no assertion criteria provided	clinical testing
Center for Precision Medicine, Meizhou People's Hospital	RCV002250483	SCV002520931	likely benign	Familial cancer of breast		no assertion criteria provided	literature only