ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.212+4T>C (rs398122652)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162796 SCV000213275 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-14 criteria provided, single submitter clinical testing The c.212+4T>C intronic variant (also known as <span style="background-color:initial">IVS5+4T>C)<span style="background-color:initial"> results from a T to C substitution 4 nucleotides after coding exon 3 in the BRCA1<span style="background-color:initial"> gene. This alteration has been reported as a variant of uncertain significance in one family from a cohort of 250 high risk, predominantly cancer affected, unrelated Israeli women (Laitman Y et al. Breast Cancer Res. Treat., 2011 Jun;127:489-95). In addition, a nearby alteration (c.212+3A>G) has been reported as a pathogenic mutation in multiple breast and/or ovarian cancer families and is a known Belgian founder mutation, though it has also been reported in German, Dutch, and French families to date (Peelen T, Am. J. Hum. Genet. 1997 May; 60(5):1041-9; Claes K, Br. J. Cancer 2004 Mar; 90(6):1244-51; Claes K, Dis. Markers 1999 Oct; 15(1-3):69-73; Janavičius R, EPMA J 2010 Sep; 1(3):397-412). <span style="background-color:initial">T<span style="background-color:initial">his nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this donor splice site; however, direct evidence is unavailable. <span style="background-color:initial">Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
GeneDx RCV000424511 SCV000520102 likely benign not specified 2015-10-09 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.
Invitae RCV000638010 SCV000759490 benign Hereditary breast and ovarian cancer syndrome 2020-10-29 criteria provided, single submitter clinical testing
Counsyl RCV000662727 SCV000785493 likely benign Breast-ovarian cancer, familial 1 2017-08-22 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162796 SCV000912057 likely benign Hereditary cancer-predisposing syndrome 2017-12-05 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353459 SCV000591249 uncertain significance not provided no assertion criteria provided clinical testing The BRCA1 c.212+4T>C variant has not been reported in the literature nor previously identified by our laboratory. This is an intronic variant residing within the consensus slice region, however it is not found to impact on splicing using the prediction programs. Another variant at c.212+3A>G reported 14 times, in BIC database, with unknown pathogenicity. In summary, based on the above information alone the clinical significance of this variant cannot be determined with certainty at the current time
Brotman Baty Institute,University of Washington RCV000662727 SCV001238074 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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