ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5495C>A (p.Ser1832Tyr) (rs138489917)

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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 RCV000132060 SCV000187122 likely benign Hereditary cancer-predisposing syndrome 2017-01-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification
Color RCV000132060 SCV000910966 likely benign Hereditary cancer-predisposing syndrome 2017-06-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000160229 SCV000591973 uncertain significance not specified 2014-12-16 criteria provided, single submitter clinical testing
GeneDx RCV000588125 SCV000210613 uncertain significance not provided 2018-12-31 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.5495C>A at the cDNA level, p.Ser1832Tyr (S1832Y) at the protein level, and results in the change of a Serine to a Tyrosine (TCT>TAT). Using alternate nomenclature, this variant would be defined as BRCA2 5723C>A. This variant was observed in one woman with breast cancer (Borg 2010). BRCA2 Ser1832Tyr was not observed in large population cohorts (Lek 2016). Since Serine and Tyrosine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Ser1832Tyr occurs at a position that is not conserved and is located in the RAD51 binding domain (Roy 2012). 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 Ser1832Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000588125 SCV000694874 uncertain significance not provided 2017-06-29 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5495C>A (p.Ser1832Tyr) variant involves the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not accessible at the time of evaluation). This variant is absent in 121052 control chromosomes in ExAC and 5/276638 chromosomes in gnomAD. This variant has been reported in one BrC patient without strong evidence for causality. one internal sample also carried a likely pathogenic variant c.5096G>A/p.R1699Q, suggesting possibly non-pathogenic role of this variant. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/VUS, all without evidence for independent evaluation. Taken together, due to lack of clinical and functional evidence, this variant is currently classified as VUS.
Invitae RCV000204966 SCV000261606 likely benign Hereditary breast and ovarian cancer syndrome 2017-11-13 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160229 SCV000600643 uncertain significance not specified 2016-11-17 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000076932 SCV000108729 likely benign Breast-ovarian cancer, familial 2 2012-09-12 no assertion criteria provided clinical testing

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