Submissions for variant NM_000059.3(BRCA2):c.2786T>C (p.Leu929Ser) (rs2227943)

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000077285	SCV000244432	benign	Breast-ovarian cancer, familial 2	2015-08-10	reviewed by expert panel	curation	IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.0000741
Invitae	RCV000167848	SCV000072068	benign	Hereditary breast and ovarian cancer syndrome	2020-12-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000120345	SCV000167346	benign	not specified	2013-10-08	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.
Michigan Medical Genetics Laboratories,University of Michigan	RCV000077285	SCV000195970	benign	Breast-ovarian cancer, familial 2	2014-11-03	criteria provided, single submitter	clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000120345	SCV000202280	benign	not specified	2014-02-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162622	SCV000213057	benign	Hereditary cancer-predisposing syndrome	2014-11-19	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
Counsyl	RCV000077285	SCV000220279	benign	Breast-ovarian cancer, familial 2	2014-04-29	criteria provided, single submitter	literature only
Illumina Clinical Services Laboratory,Illumina	RCV000077285	SCV000383657	likely benign	Breast-ovarian cancer, familial 2	2018-02-02	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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina	RCV000299643	SCV000383658	likely benign	Fanconi anemia, complementation group D1	2018-02-02	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000167848	SCV000494312	benign	Hereditary breast and ovarian cancer syndrome	2014-03-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV001283408	SCV000602853	benign	none provided	2020-08-08	criteria provided, single submitter	clinical testing
Color Health, Inc	RCV000162622	SCV000683500	benign	Hereditary cancer-predisposing syndrome	2015-09-30	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000120345	SCV000805676	benign	not specified	2016-11-02	criteria provided, single submitter	clinical testing
Research and Development, ARUP Laboratories	RCV001646101	SCV001854733	benign	Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome	2020-01-20	criteria provided, single submitter	curation
ITMI	RCV000120345	SCV000084497	not provided	not specified	2013-09-19	no assertion provided	reference population
Sharing Clinical Reports Project (SCRP)	RCV000077285	SCV000109082	benign	Breast-ovarian cancer, familial 2	2012-05-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000077285	SCV000146107	benign	Breast-ovarian cancer, familial 2	2002-05-29	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV001353953	SCV000591823	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The p.Leu929Ser variant was identified in the BIC database 41X and in the UMD database and indicated as either having no clinical significance or as being neutral, respectively. This variant is not conserved in mammals and lower organisms, although computational analysis (SIFT, AlignGVGD, BLOSUM) disagree on whether or not this variant may impact the protein. However, this information is not informative. The variant was identified in the dbSNP database (ID: rs2227943) in the HapMap-Yoruban cohort with a frequency of 0.022 and in the exome variant server database as having with a frequency of 0.004 in the African American cohort, increasing the likelihood this variant does not have clinical significance. Furthermore, Myriad genetics calls this variant as a "polymorphism" increasing the likelihood this variant does not have clinical significance. In summary, this variant meets our laboratory's criteria to be classfied as benign.
Mayo Clinic Laboratories, Mayo Clinic	RCV000656593	SCV000778655	benign	not provided	2018-02-28	no assertion criteria provided	clinical testing