ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3321A>C (p.Gln1107His) (rs397507306)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131343 SCV000186318 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,Insufficient evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Integrated Genetics/Laboratory Corporation of America RCV000780030 SCV000917035 uncertain significance not specified 2018-10-12 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3321A>C (p.Gln1107His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 234210 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3321A>C has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer without strong evidence for or against causality. Thus, this report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000794728 SCV000934154 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-24 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 1107 of the BRCA2 protein (p.Gln1107His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in a cohort of individuals with a personal and/or family history of breast and/or ovarian cancer (PMID: 29161300). ClinVar contains an entry for this variant (Variation ID: 37835). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
Mendelics RCV000031416 SCV001139061 uncertain significance Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031416 SCV000054021 uncertain significance Breast-ovarian cancer, familial 2 2008-11-11 no assertion criteria provided clinical testing

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