ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7319A>G (p.His2440Arg) (rs4986860)

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Total submissions: 26
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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) RCV000113748 SCV000245108 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 0.03049 (African), derived from 1000 genomes (2012-04-30).
Invitae RCV000167852 SCV000073200 benign Hereditary breast and ovarian cancer syndrome 2020-12-08 criteria provided, single submitter clinical testing
Counsyl RCV000113748 SCV000154046 benign Breast-ovarian cancer, familial 2 2014-01-02 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120351 SCV000202299 benign not specified 2014-12-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162498 SCV000212885 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.
Pathway Genomics RCV000113748 SCV000223769 benign Breast-ovarian cancer, familial 2 2014-10-30 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000167852 SCV000257618 likely benign Hereditary breast and ovarian cancer syndrome 2015-04-14 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000113748 SCV000267806 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 RCV000768607 SCV000324840 benign Breast and/or ovarian cancer 2016-01-26 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000305952 SCV000383764 benign Fanconi anemia, complementation group D1 2018-01-13 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 RCV000113748 SCV000383765 benign Breast-ovarian cancer, familial 2 2018-01-13 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 RCV000167852 SCV000494342 benign Hereditary breast and ovarian cancer syndrome 2014-02-28 criteria provided, single submitter clinical testing
Baylor Genetics RCV000474872 SCV000541039 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000120351 SCV000586973 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282540 SCV000602877 benign none provided 2020-06-24 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162498 SCV000683865 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 RCV000113748 SCV000744514 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120351 SCV000805759 benign not specified 2017-04-13 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034458 SCV000043225 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
ITMI RCV000120351 SCV000084503 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA2) RCV000113748 SCV000147070 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 RCV001353451 SCV000592106 benign Malignant tumor of breast no assertion criteria provided clinical testing The p.His2440Arg variant has been previously reported in the literature in 8/13066 proband chromosomes from individuals with breast and ovarian cancer, as well as in 4/280 control chromosomes (Fackenthal_2005_15744044, Gao_2000_11030417, Akbari_2011_21965345, Borg_2010_20104584, Haffty_2009_19491284). It is listed in the dbSNP database as coming from a "clinical source" (ID#: rs4986860) with a MAF score of 0.007 (1000 Genomes). The variant was identified in the ExAc Database at a frequency of 0.003 which includes 9 homozygous individuals and a 0.03 frequency in the African population. The variant was also identified in the UMD (x24), BIC (x79), Exome Server and BOCs databases. In the UMD database, the p.His2440Arg variant was found to co-occur with pathogenic mutations in BRCA1 c.IVS16+6T>C (c.4986+6T>C), as well as in BRCA2 c.2808_2811delACAA (p.Ala938ProfsX21); c.7069_7070delCT (p.Leu2357ValfsX2), increasing the likelihood that the variant is a benign alteration. This residue is not conserved in mammals and computational analyses (SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information, this variant is classified as Benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000034458 SCV000778706 likely benign not provided 2017-10-09 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162498 SCV000787948 likely benign Hereditary cancer-predisposing syndrome 2017-09-29 no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120351 SCV001906233 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120351 SCV001958535 benign not specified no assertion criteria provided clinical testing

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