ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6960G>A (p.Leu2320=) (rs373134168)

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Total submissions: 9
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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) RCV000494754 SCV000579116 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;
GeneDx RCV000123988 SCV000167386 benign not specified 2014-04-28 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 RCV000163878 SCV000214466 likely benign Hereditary cancer-predisposing syndrome 2014-10-30 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.
Invitae RCV001084861 SCV000560422 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-27 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163878 SCV000689014 likely benign Hereditary cancer-predisposing syndrome 2017-07-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000123988 SCV000695014 likely benign not specified 2019-08-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000465611 SCV001133883 likely benign not provided 2018-09-20 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000123988 SCV001158505 likely benign not specified 2019-05-22 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357829 SCV001553416 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Leu2320= variant was not identified in the literature nor was it identified in the following databases: COGR, Cosmic, BIC, ARUP Laboratories, or the Zhejiang Colon Cancer Database. The variant was identified in dbSNP (ID: rs373134168) “With Likely benign allele”, ClinVar (classified likely benign, reviewed by an expert panel (June 2017); submitters likely benign by ENIGMA, Ambry Genetics and Invitae and benign by GeneDx), Clinvitae (4x), UMD-LSDB (2x - 3-UV) and in control databases in 10 of 275770 chromosomes at a frequency of 0.00004 increasing the likelihood that this may be a low frequency variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017). Breakdown of the observations by population include Latino in 6 of 34274 chromosomes (freq: 0.0002), European Non-Finnish in 4 of 126212 chromosomes (freq: 0.00003), while the variant was not observed in the African, Ashkenazi Jewish, East Asian, South Asian, and European Finnish populations. The p.Leu2320= 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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