ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4054G>T (p.Asp1352Tyr) (rs80358655)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000031455 SCV000488911 likely benign Breast-ovarian cancer, familial 2 2016-07-20 criteria provided, single submitter clinical testing
GeneDx RCV000481701 SCV000566441 uncertain significance not provided 2017-08-23 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.4054G>T at the cDNA level, p.Asp1352Tyr (D1352Y) at the protein level, and results in the change of an Aspartic Acid to a Tyrosine (GAT>TAT). Using alternate nomenclature, this variant would be defined as BRCA2 4282G>T. This variant has been observed in at least one individual with colorectal cancer and one with breast cancer, and was predicted to be of unknown significance based on aspects of tumor pathology and genetics including receptor status, tumor grade, loss of heterozygosity, and presence of deleterious variants in trans (Spearman 2008, Yurgelun 2017). This variant was predicted by Lindor et al. (2012) to be likely neutral based on tumor pathology, clinical histories, family studies and co-occurrence with deleterious variants. BRCA2 Asp1352Tyr was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Aspartic Acid and Tyrosine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Asp1352Tyr occurs at a position that is not conserved and is located in the POLH and RAD51 binding domains (Roy 2012, Buisson 2014). 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 Asp1352Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000565185 SCV000668533 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000565185 SCV000683596 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-13 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000481701 SCV000885112 uncertain significance not provided 2017-08-25 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770723 SCV000902202 uncertain significance Breast and/or ovarian cancer 2017-04-13 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031455 SCV000054060 uncertain significance Breast-ovarian cancer, familial 2 2006-02-03 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031455 SCV000146366 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing

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