Submissions for variant NM_007294.4(BRCA1):c.2885A>G (p.Glu962Gly)

gnomAD frequency: 0.00001  dbSNP: rs780367532

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000695819	SCV000824340	uncertain significance	Hereditary breast ovarian cancer syndrome	2023-05-08	criteria provided, single submitter	clinical testing	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. 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 BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 574001). This variant is also known as c.3004A>G. This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 17262179). This variant is present in population databases (rs780367532, gnomAD 0.002%). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 962 of the BRCA1 protein (p.Glu962Gly).
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985394	SCV001133539	uncertain significance	not provided	2018-10-30	criteria provided, single submitter	clinical testing
Mendelics	RCV002249412	SCV002517954	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
University of Washington Department of Laboratory Medicine, University of Washington	RCV003158039	SCV003849282	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).
Color Diagnostics, LLC DBA Color Health	RCV003158039	SCV004360250	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-11	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with glycine at codon 962 of the BRCA1 protein. This variant is also known as 3004A>G in the literature. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in 1 individual affected with breast or ovarian cancer, a suspected hereditary breast and ovarian cancer family, and in 1 unaffected individual (PMID: 17262179, 33471991, 36881271; Leiden Open Variation Database DB-ID BRCA1_006379). This variant has been identified in 2/282752 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 Pathology and Laboratory Medicine, Sinai Health System	RCV000985394	SCV001553209	uncertain significance	not provided		no assertion criteria provided	clinical testing
Pele Pequeno Principe Research Institute, Faculdades Pequeno Principe	RCV002285401	SCV002573786	uncertain significance	Burkitt lymphoma	2021-08-03	no assertion criteria provided	clinical testing