Submissions for variant NM_000059.4(BRCA2):c.2490C>A (p.Asn830Lys)

dbSNP: rs56331088

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129537	SCV000184315	likely benign	Hereditary cancer-predisposing syndrome	2018-04-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000168037	SCV000218689	likely benign	Hereditary breast ovarian cancer syndrome	2024-12-23	criteria provided, single submitter	clinical testing
Counsyl	RCV000411773	SCV000488944	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2016-08-04	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000129537	SCV000906041	uncertain significance	Hereditary cancer-predisposing syndrome	2023-11-01	criteria provided, single submitter	clinical testing	This missense variant replaces asparagine with lysine at codon 830 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx	RCV001578080	SCV001805607	uncertain significance	not provided	2020-02-03	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 2718C>A
University of Washington Department of Laboratory Medicine, University of Washington	RCV000129537	SCV003848362	likely benign	Hereditary cancer-predisposing syndrome	2023-03-23	criteria provided, single submitter	curation	Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
All of Us Research Program, National Institutes of Health	RCV000411773	SCV004847060	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2023-11-20	criteria provided, single submitter	clinical testing	This missense variant replaces asparagine with lysine at codon 830 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.