ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.10150C>T (p.Arg3384Ter) (rs397507568)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000859426 SCV000071733 likely benign not provided 2018-12-20 criteria provided, single submitter clinical testing
GeneDx RCV000438903 SCV000518277 likely benign not specified 2016-08-18 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 RCV000565885 SCV000661329 likely benign Hereditary cancer-predisposing syndrome 2016-07-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting benign classification
Color RCV000565885 SCV000688689 likely benign Hereditary cancer-predisposing syndrome 2017-10-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000438903 SCV000918935 uncertain significance not specified 2017-12-21 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.10150C>T (p.Arg3384X) variant results in truncation of the last 35 amino acids in the last exon; therefore it is unexpected to cause nonsense-mediated decay. Truncations downstream of this position have not been classified as pathogenic by our laboratory and others in ClinVar. This variant was found in 4/277292 control chromosomes (gnomAD and publication controls) at a frequency of 0.0000144, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The BRCA2 c.9976A>T (p.Lys3326*) variant, located upstream of this variant and also in the last exon of the gene, is a known benign variant suggesting that the truncation of the last 93 amino acids of BRCA2 is unlikely to be pathogenic for breast and/or ovarian cancer. One individual reported in a database (UMD) carrying this variant also carried a premature truncating variant in BRCA1 c.2205delA (Glu736LysfsX17), further supporting for the benign outcome. This variant has been reported in several breast and/or ovarian cancer patients without strong evidence for or against pathogenicity (Han_2006, Borg_2010, Kwong_2012, Choi_2015, Kang_2015, Hayano_2016, Loizidou_2017, Kwong_2016, Zhang_2017, Yamaguchi-Kabata_2017). In one breast cancer patient carrying this variant, another missense variant in PALB2 variant was also detected (Zhang_2017). The publications classify this variant as pathogenic and uncertain significance. Multiple clinical diagnostic laboratories have recently classified this variant as likely benign (2) as well as uncertain significance (1). Taken together this variant is classified as Variant of Unknown Significance-Possibly Benign.
Mendelics RCV000112844 SCV001139288 benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000112844 SCV000145758 uncertain significance Breast-ovarian cancer, familial 2 2013-02-20 no assertion criteria provided clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000043720 SCV000586995 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-04-14 no assertion criteria provided clinical testing
3DMed Clinical Laboratory Inc RCV000677846 SCV000804006 uncertain significance Cancer of the pancreas 2017-10-09 no assertion criteria provided clinical testing

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