ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8098A>C (p.Ile2700Leu) (rs80359053)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000195382 SCV000073434 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-05-09 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with leucine at codon 2700 of the BRCA2 protein (p.Ile2700Leu). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is present in population databases (rs80359053, ExAC 0.01%). This variant has been observed in individuals n the Breast Cancer Information Core database (PMID: 10923033). However, in one of these individuals a pathogenic allele was also identified in BRCA2, which suggests that this c.8098A>C variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 52504). An algorithm developed specifically for the BRCA2 gene suggests that this missense change is likely to be tolerated (PMID: 19043619). However, this prediction has not been confirmed by published functional studies and its clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000130878 SCV000185783 uncertain significance Hereditary cancer-predisposing syndrome 2013-11-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000588136 SCV000210461 uncertain significance not provided 2016-01-18 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8098A>C at the cDNA level, p.Ile2700Leu (I2700L) at the protein level, and results in the change of an Isoleucine to a Leucine (ATA>CTA). This variant, also known as 8326A>C using alternate nomenclature, has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Ile2700Leu 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 Isoleucine and Leucine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Ile2700Leu occurs at a position that is not conserved and is located within the DNA binding domain (Borg 2010). 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 Ile2700Leu is pathogenic or benign. We consider it to be a variant of uncertain significance.
Color RCV000130878 SCV000689096 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588136 SCV000695126 uncertain significance not provided 2016-02-24 criteria provided, single submitter clinical testing
Counsyl RCV000077427 SCV000785144 uncertain significance Breast-ovarian cancer, familial 2 2017-05-12 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077427 SCV000109225 uncertain significance Breast-ovarian cancer, familial 2 2010-07-27 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077427 SCV000147273 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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