ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8225A>G (p.Asn2742Ser) (rs587782763)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132287 SCV000187372 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (benign)
Integrated Genetics/Laboratory Corporation of America RCV000587124 SCV000695120 uncertain significance not provided 2017-06-23 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.8225A>G (p.Asn2742Ser) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPsandGO not accessible at the time of evaluation). This variant is absent in 121392 control chromosomes and found in one BrC patient without strong evidence supporting causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as VUS.
Invitae RCV000460675 SCV000549495 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-07-22 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 2742 of the BRCA2 protein (p.Asn2742Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (rs587782763, ExAC no frequency). This variant has been reported in an individual affected with breast cancer (PMID: 12655560). This variant is also known as c.8453A>G in the literature. ClinVar contains an entry for this variant (Variation ID: 142847). 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 serine amino acid residue is also 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, this variant is a rare missense change that is not predicted to affect protein function. While it is absent from the population and reported in an affected individual, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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