ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5741G>C (p.Ser1914Thr) (rs80358801)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044740 SCV000072753 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-30 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 1914 of the BRCA2 protein (p.Ser1914Thr). The serine residue is weakly conserved and there is a small physicochemical difference between serine and threonine. This variant is present in population databases (rs80358801, ExAC 0.01%). This variant has been reported in an individual affected with breast/ovarian cancer (PMID: 21120943). ClinVar contains an entry for this variant (Variation ID: 51925). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
Ambry Genetics RCV000217425 SCV000276447 likely benign Hereditary cancer-predisposing syndrome 2015-06-26 criteria provided, single submitter clinical testing
GeneDx RCV000214177 SCV000279752 uncertain significance not provided 2019-01-14 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.5741G>C at the cDNA level, p.Ser1914Thr (S1914T) at the protein level, and results in the change of a Serine to a Threonine (AGC>ACC). Using alternate nomenclature, this variant would be defined as BRCA2 5969G>C. This variant was observed in 1/1,153 patients undergoing BRCA1/2 testing for a personal and/or family history of breast and/or ovarian cancer (Caux-Moncoutier 2011). BRCA2 Ser1914Thr was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Serine and Threonine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Ser1914Thr occurs at a position that is not conserved and is located in the RAD51 binding domain (Roy 2012). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA2 Ser1914Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000217425 SCV000903959 likely benign Hereditary cancer-predisposing syndrome 2017-02-09 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113474 SCV000146685 uncertain significance Breast-ovarian cancer, familial 2 2004-11-25 no assertion criteria provided clinical testing

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