Submissions for variant NM_000059.4(BRCA2):c.1714G>A (p.Val572Ile)

dbSNP: rs587782713

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000132189	SCV000187269	likely benign	Hereditary cancer-predisposing syndrome	2022-11-08	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.
Counsyl	RCV000412238	SCV000487765	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2015-11-21	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000468570	SCV000549493	uncertain significance	Hereditary breast ovarian cancer syndrome	2022-08-31	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 572 of the BRCA2 protein (p.Val572Ile). This variant is present in population databases (rs587782713, gnomAD 0.03%). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 23683081, 29021639). ClinVar contains an entry for this variant (Variation ID: 142782). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV000587521	SCV000565802	uncertain significance	not provided	2023-07-14	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Also known as 1942G>A; This variant is associated with the following publications: (PMID: 29021639, 31911673, 32377563, 29884841, 23683081, 36000185)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587521	SCV000694559	uncertain significance	not provided	2016-02-29	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000132189	SCV000911748	uncertain significance	Hereditary cancer-predisposing syndrome	2022-06-07	criteria provided, single submitter	clinical testing	This missense variant replaces valine with isoleucine at codon 572 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 been reported in an individual affected with breast cancer and a suspected hereditary breast and ovarian cancer family and also in a breast cancer case-control meta-analysis in 1/60466 cases and 2/53461 unaffected individuals (PMID: 23683081, 29021639, 33471991; Leiden Open Variation Database DB-ID BRCA2_002659). This variant has been identified in 10/251132 chromosomes 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.
Mendelics	RCV000412238	SCV001139006	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2019-05-28	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000587521	SCV002046339	uncertain significance	not provided	2020-10-26	criteria provided, single submitter	clinical testing
University of Washington Department of Laboratory Medicine, University of Washington	RCV000132189	SCV003851587	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	RCV000412238	SCV004846950	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2023-03-04	criteria provided, single submitter	clinical testing	This missense variant replaces valine with isoleucine at codon 572 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 been reported in an individual affected with breast cancer and a suspected hereditary breast and ovarian cancer family and also in a breast cancer case-control meta-analysis in 1/60466 cases and 2/53461 unaffected individuals (PMID: 23683081, 29021639, 33471991; Leiden Open Variation Database DB-ID BRCA2_002659). This variant has been identified in 10/251132 chromosomes 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.
Department of Medical and Surgical Sciences, University of Bologna	RCV000412238	SCV004228376	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-09-01	no assertion criteria provided	clinical testing	BS1(Strong)+BP1(Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)