ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9290G>A (p.Cys3097Tyr) (rs730881570)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160167 SCV000210502 uncertain significance not provided 2014-09-09 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9290G>A at the cDNA level, p.Cys3097Tyr (C3097Y) at the protein level, and results in the change of a Cysteine to a Tyrosine (TGT>TAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Cys3097Tyr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Cysteine and Tyrosine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Cys3097Tyr occurs at a position that is moderately conserved through mammals and is located in the DNA-binding domain (Borg 2010). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA2 Cys3097Tyr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000206642 SCV000259428 uncertain significance Hereditary breast and ovarian cancer syndrome 2015-07-16 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 3097 of the BRCA2 protein (p.Cys3097Tyr). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant has not been published in the literature and is not present in population databases. ClinVar contains an entry for this variant (PMID: RCV000160167). The tyrosine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In addition, 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.

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