Submissions for variant NM_000059.4(BRCA2):c.6317T>C (p.Leu2106Pro) (rs56172926)

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001085349	SCV000072914	benign	Hereditary breast and ovarian cancer syndrome	2019-12-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000131282	SCV000186251	likely benign	Hereditary cancer-predisposing syndrome	2019-01-22	criteria provided, single submitter	clinical testing	Co-occurence with mutation in same gene (phase unknown);In silico models in agreement (benign);Other data supporting benign classification
GeneDx	RCV000044901	SCV000210626	likely benign	not specified	2017-12-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV000044901	SCV000592041	benign	not specified	2013-12-24	criteria provided, single submitter	clinical testing
Color Health, Inc	RCV000131282	SCV000683771	likely benign	Hereditary cancer-predisposing syndrome	2015-03-06	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	RCV000590013	SCV000694961	likely benign	not provided	2017-01-18	criteria provided, single submitter	clinical testing	Variant summary: The BRCA2 c.6317T>C (p.Leu2106Pro) variant involves the alteration of a non-conserved nucleotide. 3/5 in silico tools predict a benign outcome for this variant. This variant was found in 10/119856 control chromosomes at a frequency of 0.0000834, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant has been reported in the literature, without strong evidence for causality. Additionally, the variant co-occurred with a pathogenic BRCA2 variant (UMD) suggesting the benign role of this variant in disease. Multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as likely benign.
Genome Diagnostics Laboratory,University Medical Center Utrecht	RCV000077370	SCV000743317	likely benign	Breast-ovarian cancer, familial 2	2015-01-09	criteria provided, single submitter	clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center	RCV000077370	SCV000744485	likely benign	Breast-ovarian cancer, familial 2	2017-05-31	criteria provided, single submitter	clinical testing
Counsyl	RCV000077370	SCV000786130	uncertain significance	Breast-ovarian cancer, familial 2	2018-03-02	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV001112565	SCV001270230	uncertain significance	Fanconi anemia, complementation group D1	2019-07-24	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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina	RCV000077370	SCV001270231	uncertain significance	Breast-ovarian cancer, familial 2	2019-07-24	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Sharing Clinical Reports Project (SCRP)	RCV000077370	SCV000109167	benign	Breast-ovarian cancer, familial 2	2011-03-17	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000077370	SCV000146823	uncertain significance	Breast-ovarian cancer, familial 2	2002-05-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto	RCV000044901	SCV000587834	benign	not specified	2014-01-31	no assertion criteria provided	research