ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5985C>T (p.Asn1995=) (rs374620036)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163574 SCV000214133 likely benign Hereditary cancer-predisposing syndrome 2014-10-23 criteria provided, single submitter clinical testing
Baylor Genetics RCV000471964 SCV000541073 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Color RCV000163574 SCV000683746 likely benign Hereditary cancer-predisposing syndrome 2016-10-13 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000418331 SCV000592018 likely benign not specified 2015-06-30 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000211013 SCV000578749 likely benign Breast-ovarian cancer, familial 2 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;
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735578 SCV000863716 likely benign Breast and/or ovarian cancer 2013-04-19 no assertion criteria provided clinical testing
GeneDx RCV000418331 SCV000512373 likely benign not specified 2017-04-04 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.
Integrated Genetics/Laboratory Corporation of America RCV000589802 SCV000694924 likely benign not provided 2017-05-01 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5985C>T (p.Asn1995Asn) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing, but ESE finder predicts that this variant may introduce an SF2/ASF ESE site at the locus. However, these predictions have yet to be confirmed by functional studies. In the literature, the variant has been identified in patient cohorts without strong evidence for association with disease (Caux-Moncoutier_HM_2011; Alsop_JCO_2012). However, this variant was identified in an internal LCA patient with a co-occurring pathogenic BRCA2 mutation (c.7988A>T [p.Glu2664Val]; classified as pathogenic in ClinVar with 8 submissions; not yet classified in GE), suggesting a benign role for the variant of interest in disease. This variant was found in the large control database ExAC at a frequency of 0.0000166 (2/120506 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). Multiple clinical diagnostic laboratories/reputable databases have classified this variant with differing interpretations, including uncertain significance, likely benign and benign (see additional comments for ClinVar entries). Taken together, this variant is classified as likely benign.
Invitae RCV000205346 SCV000260226 benign Hereditary breast and ovarian cancer syndrome 2017-12-21 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000211013 SCV000195994 uncertain significance Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589802 SCV000887861 likely benign not provided 2018-07-25 criteria provided, single submitter clinical testing

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