ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5932T>G (p.Phe1978Val)

dbSNP: rs864622526
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000204715 SCV000260981 uncertain significance Hereditary breast ovarian cancer syndrome 2023-03-10 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1978 of the BRCA2 protein (p.Phe1978Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 220443). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 RCV001799633 SCV002044288 uncertain significance not provided 2021-06-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 6160T>G; This variant is associated with the following publications: (PMID: 27535533, 9002670, 22193408)
Ambry Genetics RCV002354580 SCV002649925 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-10 criteria provided, single submitter clinical testing The p.F1978V variant (also known as c.5932T>G), located in coding exon 10 of the BRCA2 gene, results from a T to G substitution at nucleotide position 5932. The phenylalanine at codon 1978 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV002354580 SCV003850794 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).

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