ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9101A>G (p.Gln3034Arg) (rs80359164)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132242 SCV000187325 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Breast Cancer Information Core (BIC) (BRCA2) RCV000031793 SCV000147537 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000132242 SCV000689175 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-14 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000481121 SCV000592255 uncertain significance not specified 2012-03-09 criteria provided, single submitter clinical testing
GeneDx RCV000657016 SCV000566395 uncertain significance not provided 2017-06-05 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9101A>G at the cDNA level, p.Gln3034Arg (Q3034R) at the protein level, and results in the change of a Glutamine to an Arginine (CAG>CGG). Using alternate nomenclature, this variant would be defined as/ has been previously published as BRCA2 9329A>G. This variant was has been reported in at least one individual with a history of ovarian cancer and at least one individual with breast cancer (Baudi 2003, Miolo 2009). Additionally, this variant was identified as an incidental finding in at least one individual undergoing whole exome sequening (Jurgens 2015). BRCA2 Gln3034Arg was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Glutamine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Gln3034Arg occurs at a position that is not conserved and is located in the DNA binding domain (Yang 2002). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether BRCA2 Gln3034Arg is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000045716 SCV000073729 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-02-14 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 3034 of the BRCA2 protein (p.Gln3034Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs80359164, ExAC 0.003%). This variant has been reported in the literature in an individual affected with fallopian tube cancer (PMID: 12618335). ClinVar contains an entry for this variant (Variation ID: 38210). General algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD), and an algorithm developed specifically for the BRCA2 gene (PMID: 19043619), suggest that this missense change is likely to be tolerated.  The arginine 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. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000031793 SCV000054401 uncertain significance Breast-ovarian cancer, familial 2 2009-10-09 no assertion criteria provided clinical testing

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