Submissions for variant NM_000059.3(BRCA2):c.6325G>A (p.Val2109Ile) (rs79456940)

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
3DMed Clinical Laboratory Inc	RCV000677821	SCV000803981	uncertain significance	Cancer of the pancreas	2018-05-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000129753	SCV000184560	likely benign	Hereditary cancer-predisposing syndrome	2017-11-29	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: Other data supporting benign classification,In silico models in agreement (benign),Co-occurence with mutation in same gene (phase unknown)
Biesecker Lab/Clinical Genomics Section,National Institutes of Health	RCV000034454	SCV000043221	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113573	SCV000146827	uncertain significance	Breast-ovarian cancer, familial 2	2002-05-29	no assertion criteria provided	clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics	RCV000034454	SCV000609564	likely benign	not provided	2017-03-29	criteria provided, single submitter	clinical testing
Color	RCV000129753	SCV000902701	likely benign	Hereditary cancer-predisposing syndrome	2015-11-03	criteria provided, single submitter	clinical testing
Counsyl	RCV000113573	SCV000784864	likely benign	Breast-ovarian cancer, familial 2	2017-01-18	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV000044913	SCV000592044	benign	not specified	2013-11-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000044913	SCV000210386	likely benign	not specified	2017-04-06	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.
Illumina Clinical Services Laboratory,Illumina	RCV000406166	SCV000383740	likely benign	Fanconi anemia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000195307	SCV000383741	likely benign	Hereditary breast and ovarian cancer syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	RCV000034454	SCV000694965	likely benign	not provided	2016-12-01	criteria provided, single submitter	clinical testing	Variant summary: The BRCA2 c.6325G>A (p.Val2109Ile) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 38/122036 control chromosomes, predominantly observed in the East Asian subpopulation at a frequency of 0.0038354 (33/8604). This frequency is about 5 times the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. The variant has been reported in numerous affected individuals in the literature, mostly of Asian origin, without strong evidence for causality. BIC reports the variant in 2 individuals who also carry pathogenic variants (BRCA1 c.4163_4164insA; BRCA2 c.9076C>T), also supportive of a benign outcome. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign, although some classify it as a VUS. Taken together, this variant is classified likley benign.
Invitae	RCV000195307	SCV000072926	benign	Hereditary breast and ovarian cancer syndrome	2017-12-29	criteria provided, single submitter	clinical testing
Laboratory of Molecular Diagnosis of Cancer,West China Hospital, Sichuan University	RCV000240685	SCV000265952	uncertain significance	Neoplasm of the breast	2015-11-01	criteria provided, single submitter	research
Sharing Clinical Reports Project (SCRP)	RCV000113573	SCV000297542	benign	Breast-ovarian cancer, familial 2	2008-10-28	no assertion criteria provided	clinical testing