ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2783G>A (p.Gly928Asp) (rs202004680)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000221501 SCV000276391 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-11 criteria provided, single submitter clinical testing The p.G928D variant (also known as c.2783G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 2783. The glycine at codon 928 is replaced by aspartic acid, an amino acid with similar properties. This variant was detected as a secondary finding in 1 out of 572 ClinSeq participants, unselected for personal or family history of cancer, who underwent exome sequencing; however, the clinical information for this particular individual was not provided (Johnston JJ et al. Am. J. Hum. Genet., 2012 Jul;91:97-108). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000227370 SCV000289766 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-08-02 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 928 of the BRCA1 protein (p.Gly928Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with breast cancer (PMID: 16267036). ClinVar contains an entry for this variant (Variation ID: 41813). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0). The aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000034736 SCV000600302 uncertain significance not provided 2019-08-18 criteria provided, single submitter clinical testing
Color Health, Inc RCV000221501 SCV001347079 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-25 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001659937 SCV001878270 likely benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034736 SCV000043172 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.

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