ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1211A>G (p.Asn404Ser) (rs80358414)

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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 RCV000571012 SCV000668740 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000571012 SCV000683406 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586358 SCV000694521 uncertain significance not provided 2017-05-26 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1211A>G (p.Asn404Ser) variant involves the alteration of a conserved nucleotide. 4/5 in silico tools predict a benign outcome for this variant. This variant is absent in 120776 control chromosomes. This variant has been detected twice in a cohort of 507 Chinese breast cancer patients without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, due to lack of clinical and functional evidence, this variant is currently classified as VUS.
Invitae RCV000472702 SCV000549879 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-12 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 404 of the BRCA2 protein (p.Asn404Ser). 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 (ExAC no frequency). This variant has been reported in individuals affected with breast cancer (PMID: 27257965). ClinVar contains an entry for this variant (Variation ID: 224455). 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 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 affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory of Molecular Diagnosis of Cancer,West China Hospital, Sichuan University RCV000240794 SCV000265929 uncertain significance Neoplasm of the breast 2015-11-01 criteria provided, single submitter research
Mendelics RCV000472702 SCV000838753 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing

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