ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.905C>A (p.Thr302Asn) (rs80359158)

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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 RCV000564157 SCV000668753 uncertain significance Hereditary cancer-predisposing syndrome 2017-02-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000564157 SCV000684021 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-01 criteria provided, single submitter clinical testing
GeneDx RCV000758969 SCV000210260 uncertain significance not provided 2015-12-02 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.905C>A at the cDNA level, p.Thr302Asn (T302N) at the protein level, and results in the change of a Threonine to an Asparagine (ACC>AAC). This variant, also known as BRCA2 1133C>A by alternate nomenclature, has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Thr302Asn was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. Since Threonine and Asparagine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Thr302Asn occurs at a position that is not conserved across species and is not located in a known functional domain. In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. Based on the currently available information, we consider BRCA2 Thr302Asn to be a variant of uncertain significance.
Invitae RCV000197152 SCV000254223 uncertain significance Hereditary breast and ovarian cancer syndrome 2015-04-17 criteria provided, single submitter clinical testing This sequence change replaces threonine with asparagine at codon 302 of the BRCA2 protein (p.Thr302Asn). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and asparagine. This variant has not been published in the literature and is present in population databases (rs80359158, 0.001%). ClinVar contains entries for this variant (RCV000082999, RCV000160033). 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, this is a rare missense change that is not predicted to affect protein function or cause disease. However the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758969 SCV000887954 uncertain significance not provided 2018-04-16 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000082999 SCV000115073 uncertain significance Breast-ovarian cancer, familial 2 2007-01-04 no assertion criteria provided clinical testing

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