ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9076C>G (p.Gln3026Glu) (rs80359159)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045705 SCV000073718 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-07 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 3026 of the BRCA2 protein (p.Gln3026Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs80359159, ExAC 0.003%). This variant has been observed in individuals affected with breast and/or ovarian cancer (PMID: 12161607, 27376475). This variant is also known as c.9304C>G in the literature. ClinVar contains an entry for this variant (Variation ID: 52742). This variant has been reported not to substantially affect BRCA2 protein function (PMID: 29884841). 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.
Ambry Genetics RCV000129636 SCV000184431 uncertain significance Hereditary cancer-predisposing syndrome 2014-12-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
GeneDx RCV000520875 SCV000617886 uncertain significance not provided 2017-05-09 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9076C>G at the cDNA level, p.Gln3026Glu (Q3026E) at the protein level, and results in the change of a Glutamine to a Glutamic Acid (CAG>GAG). Using alternate nomenclature, this variant has been previously published as BRCA2 9304C>G. This variant has been observed in at least two individuals with suspected Hereditary Breast and Ovarian Cancer (Kauff 2002, Schenkel 2016). BRCA2 Gln3026Glu 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 Glutamic Acid differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Gln3026Glu 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 evidence, it is unclear whether BRCA2 Gln3026Glu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Breast Cancer Information Core (BIC) (BRCA2) RCV000114041 SCV000147528 uncertain significance Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing

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