ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.135-23CTTT[2] (rs878854931)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001080285 SCV000289741 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-05 criteria provided, single submitter clinical testing
GeneDx RCV000487231 SCV000572442 likely benign not specified 2017-09-13 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 RCV000776492 SCV000912074 likely benign Hereditary cancer-predisposing syndrome 2018-06-13 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000487231 SCV001363935 likely benign not specified 2019-11-18 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.135-15_135-12delCTTT alters four non-conserved nucleotides located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 246264 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.135-15_135-12delCTTT has been reported in the literature as a "rare-neutral variant" in individuals affected with Hereditary Breast and Ovarian Cancer (example, Judkins_2005, Vreeswijk_2008, Mohammadi_2009). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. At-least one co-occurrence with another pathogenic variant(s) has been reported at our laboratory (BRCA2 c.7758G>A, p.W2586X), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on splicing and showed no damaging effect of this variant on RNA splicing (Vreeswijk_2008). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was re-classified as likely benign.

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