ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7413A>G (p.Thr2471=) (rs138067005)

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Total submissions: 11
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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) RCV000495312 SCV000579060 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;
Ambry Genetics RCV000213502 SCV000273910 likely benign Hereditary cancer-predisposing syndrome 2015-02-16 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV000417816 SCV000515759 benign not specified 2015-06-23 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.
Baylor Genetics RCV000457254 SCV000541057 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Invitae RCV001083358 SCV000560482 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000417816 SCV000695059 likely benign not specified 2019-08-21 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000495312 SCV000744516 likely benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586071 SCV000887914 likely benign not provided 2019-10-25 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000586071 SCV000892067 likely benign not provided 2019-05-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000213502 SCV000903484 likely benign Hereditary cancer-predisposing syndrome 2016-06-15 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357473 SCV001552955 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Thr2471= variant was identified in 3 of 3698 proband chromosomes (frequency: 0.001) from individuals or families with unilateral breast cancer or hereditary breast cancer (Borg 2010, Claes 2004). The variant was also identified in dbSNP (ID: rs138067005) as "With Likely benign allele" , ClinVar (classified as benign by GeneDx and Baylor Miraca Genetics Laboratories Study description; as likely benign by Invitae, Ambry Genetics, Enigma and DNA and Cytogenetics Diagnostics Unit, Erasmus Medical Center; as uncertain significance by Integrated Genetics/Laboratory Corporation of America), Clinvitae, LOVD 3.0 (4x conflicting interpretation of pathogenicity), and in UMD-LSDB (1x as unclassified variant) databases. The variant was not identified in GeneInsight-COGR, Cosmic, BIC Database, ARUP Laboratories, or Zhejiang University Database databases. The variant was identified in control databases in 8 of 245878 chromosomes at a frequency of 0.00003 (Genome Aggregation Database Feb 27, 2017). The variant observed in European population in 8 of 111442 chromosomes (freq: 0.0001), while the variant was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Thr2471= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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