ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6953G>A (p.Arg2318Gln) (rs80358921)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131677 SCV000186713 likely benign Hereditary cancer-predisposing syndrome 2017-08-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification
Breast Cancer Information Core (BIC) (BRCA2) RCV000077390 SCV000146980 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131677 SCV000903879 likely benign Hereditary cancer-predisposing syndrome 2016-05-02 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000168594 SCV000588112 likely benign not specified 2017-04-20 criteria provided, single submitter clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735593 SCV000863731 uncertain significance Breast and/or ovarian cancer no assertion criteria provided clinical testing
GeneDx RCV000656799 SCV000210409 uncertain significance not provided 2017-05-16 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6953G>A at the cDNA level, p.Arg2318Gln (R2318Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant, previously reported as BRCA2 7181G>A using alternate nomenclature, has been observed in several individuals with breast, ovarian, prostate, and pancreatic cancer (Chenevix-Trench 2006, Kote-Jarai 2011, Alsop 2012, Couch 2015, Grant 2015, Dos Santos Vidal 2016). A functional study found this variant showed decreased cell survival and a higher rate of apoptosis in response to cisplatin as compared to wild-type (Warren 2011). However, this variant was predicted by Lindor et al. (2012) to be likely not pathogenic based on tumor pathology, clinical histories, family studies, and co-occurrence with deleterious variants. BRCA2 Arg2318Gln was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Arg2318Gln occurs at a position that is conserved across species and is not located in a known functional domain. 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 Arg2318Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000203633 SCV000073109 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-12 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077390 SCV000109187 likely benign Breast-ovarian cancer, familial 2 2012-03-29 no assertion criteria provided clinical testing

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