ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1804G>A (p.Gly602Arg) (rs80358466)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077267 SCV000244426 benign Breast-ovarian cancer, familial 2 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000000101
Invitae RCV000195301 SCV000071906 benign Hereditary breast and ovarian cancer syndrome 2018-01-09 criteria provided, single submitter clinical testing
GeneDx RCV000168552 SCV000210569 likely benign not specified 2017-11-15 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.
Ambry Genetics RCV000162545 SCV000212949 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Counsyl RCV000077267 SCV000488588 benign Breast-ovarian cancer, familial 2 2016-05-03 criteria provided, single submitter clinical testing
Color RCV000162545 SCV000683452 likely benign Hereditary cancer-predisposing syndrome 2015-02-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587883 SCV000694568 likely benign not provided 2017-01-23 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1804G>A (p.Gly602Arg) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict a benign outcome for this variant. This variant was found in 3/118422 control chromosomes at a frequency of 0.0000253, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). This variant has been reported in multiple individuals affected with breast and/or ovarian cancer without strong evidence for causality. In a family, unaffected mother of the proband also carried this variant, suggesting a putative lack of cosegregation with disease (Carney_2010). Multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign/VUS, all without evidence for independent evaluation. A clinical database (BIC) has reported two cases with co-occurrence of variant of interest and a pathogenic BRCA1 variant (c.5266dupC (p.Gln1756Profs) and c.2679_2682delGAAA (p.Lys893Asnfs), respectively), strongly supporting the benign role of this variant. Systematic genetic assessment and/or multifactorial probability model has also suggested the variant to have a high odds in favor of neutrality or low odds in favor of pathogenicity (Easton_2007; Lindor_2012). Taken together, especially considering its co-occurrence with multiple disease variants and findings from multifactorial probability model, this variant is classified as Likely Benign.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000077267 SCV000743266 likely benign Breast-ovarian cancer, familial 2 2017-07-28 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077267 SCV000744418 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077267 SCV000109064 benign Breast-ovarian cancer, familial 2 2010-01-15 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077267 SCV000145944 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000077267 SCV000733235 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing

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