ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8014A>G (p.Ile2672Val) (rs80359037)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000225751 SCV000073400 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-02 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 2672 of the BRCA2 protein (p.Ile2672Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs80359037, ExAC 0.01%). This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 25682074, 27062684). ClinVar contains an entry for this variant (Variation ID: 38135). An experimental study has shown that this missense change does not significantly disrupt the homology-directed DNA repair activity of the BRCA2 protein (PMID: 29394989, 29884841). 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 RCV000129989 SCV000184813 likely benign Hereditary cancer-predisposing syndrome 2017-08-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Other data supporting benign classification
GeneDx RCV000045387 SCV000210664 likely benign not specified 2018-01-08 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color RCV000129989 SCV000689090 likely benign Hereditary cancer-predisposing syndrome 2017-02-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587957 SCV000695123 likely benign not provided 2017-01-24 criteria provided, single submitter clinical testing Variant summary: The BRCA2 8014A>G (p.Ile2672Val) variant, alternatively also known as 8242A>G, involves the alteration of a non-conserved nucleotide and is predicted to be damaging by 2/3 in silico tools (SNPs&GO not captured due to low reliability index). Based on the protein likelihood ratio calculation this variant was predicted to be neutral (Karching et al., 2008). This variant was found in 1/120556 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). This variant has been reported in several HBOC patients/families in literature and clinical databases. This variant was found not to cosegregate with disease amongst nine unrelated families (Miller-Samuel et al, 2011). Although details of genotypic and phenotypic information is not provided for family members, this study strongly supports for the benign outcome. In addition, the variant's co-occurrence with another BRCA1/2 pathogenic variant has also been reported (Azzollini_2016), further supporting the benign outcome. Multiple clinical diagnostic laboratories/reputable databases have classified this variant as uncertain significance (3) as well as likely benign (3). Taken together, this variant is currently classified as Likely Benign.
Sharing Clinical Reports Project (SCRP) RCV000031717 SCV000054324 likely benign Breast-ovarian cancer, familial 2 2011-11-17 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031717 SCV000147250 uncertain significance Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
True Health Diagnostics RCV000129989 SCV000805247 likely benign Hereditary cancer-predisposing syndrome 2018-05-03 no assertion criteria provided clinical testing

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