ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.10220A>G (p.Asn3407Ser) (rs80358401)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129602 SCV000184387 likely benign Hereditary cancer-predisposing syndrome 2019-01-29 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
GeneDx RCV000212294 SCV000210700 likely benign not specified 2015-03-27 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Counsyl RCV000112850 SCV000488149 uncertain significance Breast-ovarian cancer, familial 2 2016-03-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000212294 SCV000694500 uncertain significance not specified 2021-04-06 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.10220A>G (p.Asn3407Ser) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250846 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.10220A>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign, n=3; VUS, n=2). Based on the evidence outlined above, the variant was classified as uncertain significance.
Color Health, Inc RCV000129602 SCV000906968 likely benign Hereditary cancer-predisposing syndrome 2018-08-30 criteria provided, single submitter clinical testing
Invitae RCV001370256 SCV001566726 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-07-20 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 3407 of the BRCA2 protein (p.Asn3407Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs80358401, ExAC 0.002%). This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 51055). 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 and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional 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.
Breast Cancer Information Core (BIC) (BRCA2) RCV000112850 SCV000145767 uncertain significance Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000589028 SCV000592317 uncertain significance not provided no assertion criteria provided clinical testing

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