ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1627C>T (p.His543Tyr) (rs80358446)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166042 SCV000216803 uncertain significance Hereditary cancer-predisposing syndrome 2014-09-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
GeneDx RCV000485437 SCV000571832 uncertain significance not provided 2016-09-27 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.1627C>T at the cDNA level, p.His543Tyr (H543Y) at the protein level, and results in the change of a Histidine to a Tyrosine (CAT>TAT). Using alternate nomenclature, this variant would be defined as BRCA2 1855C>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 His543Tyr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Histidine and Tyrosine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 His543Tyr occurs at a position that is not conserved and is not located in a known functional domain (Cole 2011). 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 His543Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000166042 SCV000906027 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-22 criteria provided, single submitter clinical testing

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