ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5538G>A (p.Gln1846=) (rs80356849)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112700 SCV000578244 likely benign Breast-ovarian cancer, familial 1 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02;
Invitae RCV000588004 SCV000077056 likely benign not provided 2018-12-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV000164404 SCV000215040 likely benign Hereditary cancer-predisposing syndrome 2014-10-22 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000496446 SCV000591639 likely benign not specified 2014-05-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588004 SCV000699271 likely benign not provided 2016-03-22 criteria provided, single submitter clinical testing Variant Summary: The BRCA1 c.5538G>A variant involves the alteration of a non-conserved nucleotide resulting in a synonymous change. 3/5 in silico tools via Alamut predict no significant effect on splicing. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.0008% which does not exceed the maximal expected allele frequency for a pathogenic variant in BRCA1 (0.10%). The variant was reported in the literature in an individual who also carried a pathogenic BRCA1 variant on opposite allele (c.66_67delAG; Diez_2003), strongly suggesting the benign nature of the variant. Additionally, functional studies show the variant to have no effect on splicing (Houdayer_2012). Multiple reputable clinical labs have classified the variant as "likely benign." Therefore, this variant was classified as Likely Benign.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112700 SCV000145573 uncertain significance Breast-ovarian cancer, familial 1 1997-03-11 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496446 SCV000587521 benign not specified 2014-01-31 no assertion criteria provided research

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