Submissions for variant NM_000059.3(BRCA2):c.5882G>A (p.Ser1961Asn) (rs80358820)

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000044784	SCV000072797	likely benign	not provided	2019-03-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000128953	SCV000172831	likely benign	Hereditary cancer-predisposing syndrome	2018-11-21	criteria provided, single submitter	clinical testing	In silico models in agreement (benign);Other strong data supporting benign classification
GeneDx	RCV000439783	SCV000512372	likely benign	not specified	2018-01-10	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.
Integrated Genetics/Laboratory Corporation of America	RCV000439783	SCV000694914	uncertain significance	not specified	2019-01-21	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.5882G>A (p.Ser1961Asn) results in a conservative amino acid change located in the BRCA2 repeat region, between the repeats BRC6 and BRC7 (IPR002093) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 246088 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.5882G>A has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Blay_2013, Infante_2006, Velasco_2005). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variant(s) have been reported (BRCA1 c.3331_3334delCAAG, p.Gln1111fsX5 in the BIC database), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four other ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant, three times as likely benign and once as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Counsyl	RCV000031585	SCV000784831	uncertain significance	Breast-ovarian cancer, familial 2	2017-01-04	criteria provided, single submitter	clinical testing
Color	RCV000128953	SCV000903520	benign	Hereditary cancer-predisposing syndrome	2016-12-21	criteria provided, single submitter	clinical testing
Mendelics	RCV000031585	SCV001139129	likely benign	Breast-ovarian cancer, familial 2	2019-05-28	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000031585	SCV000054191	benign	Breast-ovarian cancer, familial 2	2012-03-12	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000031585	SCV000146722	uncertain significance	Breast-ovarian cancer, familial 2	2002-06-20	no assertion criteria provided	clinical testing