ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6966G>T (p.Met2322Ile) (rs80358924)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000509983 SCV000608122 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Intact protein function observed in appropriate functional assay(s),Insufficient evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000077391 SCV000146983 uncertain significance Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
GeneDx RCV000255458 SCV000321479 uncertain significance not provided 2015-06-01 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6966G>T at the cDNA level, p.Met2322Ile (M2322I) at the protein level, and results in the change of a Methionine to an Isoleucine (ATG>ATT). This variant, also known as 7194G>T using alternate nomenclature, has been reported in an individual with breast cancer as well as her affected mother. The breast tumor samples from these 2 individuals did not exhibit loss of heterozygosity (Cochran 2014). BRCA2 Met2322Ile was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Methionine and Isoleucine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Met2322Ile occurs at a position that is not conserved and is not located in a known functional domain (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA2 Met2322Ile is pathogenic or benign. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077391 SCV000296532 uncertain significance Breast-ovarian cancer, familial 2 2016-04-23 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077391 SCV000109188 uncertain significance Breast-ovarian cancer, familial 2 2012-02-17 no assertion criteria provided clinical testing

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