ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9730G>A (p.Val3244Ile) (rs11571831)

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Total submissions: 25
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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) RCV000114158 SCV000245313 benign Breast-ovarian cancer, familial 2 2015-01-12 reviewed by expert panel curation Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.02642 (African), derived from 1000 genomes (2012-04-30).
Invitae RCV000167853 SCV000073906 benign Hereditary breast and ovarian cancer syndrome 2020-12-08 criteria provided, single submitter clinical testing
Counsyl RCV000114158 SCV000154086 benign Breast-ovarian cancer, familial 2 2014-03-18 criteria provided, single submitter literature only
Ambry Genetics RCV000128917 SCV000172784 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing This alteration is classified as 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120377 SCV000202308 benign not specified 2015-04-29 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000167853 SCV000257621 likely benign Hereditary breast and ovarian cancer syndrome 2015-04-14 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000114158 SCV000267832 benign Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768643 SCV000324841 benign Breast and/or ovarian cancer 2015-12-10 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000313558 SCV000383804 benign Fanconi anemia, complementation group D1 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000114158 SCV000383805 benign Breast-ovarian cancer, familial 2 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000167853 SCV000494347 benign Hereditary breast and ovarian cancer syndrome 2014-04-14 criteria provided, single submitter clinical testing
Baylor Genetics RCV000469360 SCV000541041 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000120377 SCV000586992 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282539 SCV000602873 benign none provided 2020-06-24 criteria provided, single submitter clinical testing
Color Health, Inc RCV000128917 SCV000684089 benign Hereditary cancer-predisposing syndrome 2015-03-05 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000114158 SCV000744793 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000128917 SCV000747800 likely benign Hereditary cancer-predisposing syndrome 2018-01-16 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120377 SCV000805801 benign not specified 2017-04-13 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034473 SCV000043238 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
ITMI RCV000120377 SCV000084529 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA2) RCV000114158 SCV000147705 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353392 SCV000592306 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Val3244Ile variant was identified in the literature in 5/7922 proband chromosomes (frequency: 0.001) from individuals with breast cancer; however, no control chromosomes were tested to establish the frequency of the variant in the general population (Borg 2010, Caux-Moncoutier 2011; Haffty 2009). The variant was also identified in the BIC database (73X with unknown clinical importance) and in UMD (28X as an unclassified variant) where it was listed to co-occur with a pathogenic mutation in BRCA1 (c.2551G>T (p.Glu851X)), increasing the likelihood that this variant may not have clinical importance. The p.Val3244 residue is not conserved in mammals, and the variant amino acid Isoleucine (Ile) is present in macaque at this position, increasing the likelihood that an alteration to this residue may not have functional significance. Computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM) do not predict any effect on the protein function; however, this information is not predictive enough to rule out pathogenicity. The variant is listed in dbSNP as coming from a "clinical source" (ID#: rs11571831) with a minor allele frequency of 0.006 (1000 Genomes). It was also identified in the NHLBI Exome Sequencing Project with a frequency of 0.025 in African American alleles, and in several HapMap populations including HapMap-YRI (frequency: 0.032), HapMap-JPT (frequency: 0.03) and HapMap-CEU (frequency: 0.033), increasing the likelihood that this is a low frequency benign polymorphism in certain populations of origin. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000034473 SCV000778725 likely benign not provided 2017-12-23 no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120377 SCV001906184 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120377 SCV001956446 benign not specified no assertion criteria provided clinical testing

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