ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2416G>A (p.Ala806Thr) (rs80357144)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000047832 SCV000075845 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-11 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 806 of the BRCA1 protein (p.Ala806Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs80357144, ExAC 0.001%). This variant has been observed in individuals affected with breast cancer or at risk for hereditary breast and ovarian cancer (PMID: 20104584, 21520273, 20127978). ClinVar contains an entry for this variant (Variation ID: 54563). Experimental in vitro studies have shown that this variant does not affect the homologous recombination activity of the BRCA1 protein (PMID: 26689913). 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.
GeneDx RCV000212167 SCV000209939 likely benign not specified 2017-10-02 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.
Ambry Genetics RCV000218307 SCV000274017 likely benign Hereditary cancer-predisposing syndrome 2015-02-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000212167 SCV000698950 uncertain significance not specified 2019-05-03 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2416G>A (p.Ala806Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250528 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2416G>A has been reported in the literature in individuals affected with breast cancer (e.g. Borg_2010) without strong evidence of causality. Therefore, these reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. In addition, a functional study reports that this variant has no impact on homologous recombination activity of BRCA1 protein (Lu_2015). Three submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation ((1x uncertain significance and 2x likely benign). Based on the evidence outlined above, the variant was classified as VUS - possibly benign until additional clinical and functional evidence becomes available.
Color RCV000218307 SCV000909344 likely benign Hereditary cancer-predisposing syndrome 2018-05-31 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077517 SCV000109318 likely benign Breast-ovarian cancer, familial 1 2009-04-30 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077517 SCV000144423 uncertain significance Breast-ovarian cancer, familial 1 2001-10-29 no assertion criteria provided clinical testing

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