ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2981C>T (p.Ala994Val) (rs398122758)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160052 SCV000210299 uncertain significance not provided 2017-03-29 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.2981C>T at the cDNA level, p.Ala994Val (A994V) at the protein level, and results in the change of an Alanine to a Valine (GCA>GTA). Using alternate nomenclature, this variant would be defined as BRCA2 3209C>T. This variant was observed two patients with serous ovarian cancer (Li 2013). BRCA2 Ala994Val was not observed at a significant frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Alanine and Valine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Ala994Val occurs at a position that is not conserved 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 Ala994Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000165816 SCV000216563 uncertain significance Hereditary cancer-predisposing syndrome 2014-10-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Sharing Clinical Reports Project (SCRP) RCV000077701 SCV000109504 uncertain significance Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Invitae RCV000122905 SCV000166163 uncertain significance Hereditary breast and ovarian cancer syndrome 2014-06-11 no assertion criteria provided clinical testing The interpretation for this sequence variant was made by Invitae based on the ACMG guidelines.

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