ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3462C>T (p.Thr1154=) (rs4986856)

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Total submissions: 8
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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) RCV000495110 SCV000579168 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; http://priors.hci.utah.edu/PRIORS/).
Ambry Genetics RCV000163356 SCV000213890 likely benign Hereditary cancer-predisposing syndrome 2014-10-15 criteria provided, single submitter clinical testing In silico models in agreement (benign);Synonymous alterations with insufficient evidence to classify as benign
Invitae RCV001080150 SCV000260166 benign Hereditary breast and ovarian cancer syndrome 2020-12-01 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001281701 SCV000600551 benign not specified 2020-01-30 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163356 SCV000683558 likely benign Hereditary cancer-predisposing syndrome 2016-08-30 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679168 SCV000805693 likely benign not provided 2017-05-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001281701 SCV001623319 likely benign not specified 2021-04-25 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355144 SCV001549938 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Thr1154= variant was identified in 4 of 3732 proband chromosomes (frequency: 0.001) from individuals or families with breast or ovarian cancer and was not identified in 334 control chromosomes from healthy individuals (Caux-Moncoutier 2009, Han S-H 2006, Kim 2006). The variant was also identified in dbSNP (ID: rs4986856) as "With Likely benign allele", ClinVar (classified as likely benign by Ambry Genetics, Invitae, Color Genomics and two clinical laboratories), LOVD 3.0 (2x), and in UMD-LSDB (3x as unclassified variant). The variant was not identified in COGR, Cosmic, BIC Database, ARUP Laboratories, or Zhejiang University Database. The variant was identified in control databases in 12 of 276656 chromosomes at a frequency of 0.00004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 24016 chromosomes (freq: 0.00004), European in 11 of 126230 chromosomes (freq: 0.00009), while the variant was not observed in the Other, Latino, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Thr1154= 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) 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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