ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6550C>G (p.Gln2184Glu) (rs80358887)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001085289 SCV000072995 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129780 SCV000184589 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-17 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000587939 SCV000210393 uncertain significance not provided 2016-04-27 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6550C>G at the cDNA level, p.Gln2184Glu (Q2184E) at the protein level, and results in the change of a Glutamine to a Glutamic Acid (CAG>GAG). Using alternate nomenclature, this variant would be defined as BRCA2 6778C>G. This variant was observed in a patient with early onset breast cancer (El Saghir 2015). BRCA2 Gln2184Glu was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Glutamine and Glutamic Acid differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Gln2184Glu occurs at a position that is not conserved and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA2 Gln2184Glu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000113608 SCV000488122 uncertain significance Breast-ovarian cancer, familial 2 2016-02-19 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001175370 SCV000694980 uncertain significance not specified 2019-09-26 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.6550C>G (p.Gln2184Glu) 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 1.2e-05 in 245924 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.6550C>G, has been reported in the literature in at least one individual affected with breast cancer (El Saghir_2015). The 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. Five other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (3x VUS, 2x Likely benign). Based on the evidence outlined above, the variant was classified as uncertain significance.
Color RCV000129780 SCV000910911 likely benign Hereditary cancer-predisposing syndrome 2016-08-18 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113608 SCV000146882 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000113608 SCV000297544 likely benign Breast-ovarian cancer, familial 2 2010-03-11 no assertion criteria provided clinical testing

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