Submissions for variant NM_000059.3(BRCA2):c.3814A>G (p.Met1272Val) (rs80358624)

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000203673	SCV000072284	likely benign	Hereditary breast and ovarian cancer syndrome	2017-11-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000130732	SCV000185623	likely benign	Hereditary cancer-predisposing syndrome	2018-03-20	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: In silico models in agreement (benign),Other strong data supporting benign classification
GeneDx	RCV000044271	SCV000210596	likely benign	not specified	2017-11-06	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.
Counsyl	RCV000083100	SCV000489068	uncertain significance	Breast-ovarian cancer, familial 2	2016-08-12	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV000044271	SCV000591876	uncertain significance	not specified	2015-03-10	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	RCV000588689	SCV000694720	uncertain significance	not provided	2017-08-17	criteria provided, single submitter	clinical testing	Variant summary: The BRCA2 c.3814A>G (p.Met1272Val) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in the large control database ExAC at a frequency of 0.0000191 (2/104976 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant has been observed in affected individuals in the literature without strong evidence for causality (such as co-occurrence and cosegregation data). In ClinVar, multiple clinical diagnostic laboratories/reputable databases have classified this variant with different interpretations, including uncertain significance and likely benign. Taken together, this variant is classified as VUS.
Color	RCV000130732	SCV000910980	benign	Hereditary cancer-predisposing syndrome	2017-05-02	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000083100	SCV000115174	benign	Breast-ovarian cancer, familial 2	2012-05-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000083100	SCV000146302	uncertain significance	Breast-ovarian cancer, familial 2	2004-02-20	no assertion criteria provided	clinical testing