ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4241C>T (p.Thr1414Met) (rs70953664)

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Total submissions: 21
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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) RCV000113286 SCV000245031 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 0.0122 (African), derived from 1000 genomes (2012-04-30).
Invitae RCV000167832 SCV000072388 benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120327 SCV000202286 benign not specified 2015-05-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162766 SCV000213243 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.
Counsyl RCV000113286 SCV000220272 benign Breast-ovarian cancer, familial 2 2014-04-25 criteria provided, single submitter literature only
Vantari Genetics RCV000162766 SCV000267016 likely benign Hereditary cancer-predisposing syndrome 2015-12-21 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000113286 SCV000267764 benign Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000113286 SCV000383695 likely benign Breast-ovarian cancer, familial 2 2018-10-29 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000346290 SCV000383696 likely benign Fanconi anemia, complementation group D1 2018-10-29 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000167832 SCV000494351 benign Hereditary breast and ovarian cancer syndrome 2014-03-06 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000113286 SCV000575755 likely benign Breast-ovarian cancer, familial 2 2016-01-29 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000120327 SCV000593716 likely benign not specified 2017-02-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283466 SCV000602745 benign none provided 2019-11-08 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162766 SCV000683605 likely benign Hereditary cancer-predisposing syndrome 2015-03-06 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000113286 SCV000744453 likely benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
ITMI RCV000120327 SCV000084479 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA2) RCV000113286 SCV000146394 benign Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353946 SCV000591896 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Thr1414Met variant was identified in 4 of 7918 chromosomes (frequency: 0.001) from individuals with breast or ovarian cancer, and in 1 of 148 control chromosomes (frequency: 0.007) from these studies (Borg 2010, Fackenthal 2005, Lee 2007, Palomba 2009). It is listed in dbSNP (ID#: rs70953664) with a “global minor allele frequency" of 0.003 (1000 Genomes), and in the Exome Variant Server ESP project with a frequency of 0.007 in African American alleles, increasing the likelihood that this is a low frequency benign variant in certain populations of origin. This variant was identified in LOVD, in BIC 38X with no clinical importance, and in UMD 3X as a “neutral” variant where it was reported to co-occur with a known BRCA2 pathogenic mutation (BRCA2 c.6159delT (p.Ala2054LeufsX16)), further increasing the likelihood that this variant is benign. The p.Thr1414 residue is not conserved through evolution, with the variant amino acid Methionine (Met) present in mouse, rat and cat; and computational analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000656603 SCV000778673 likely benign not provided 2017-07-24 no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120327 SCV001905929 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120327 SCV001957277 benign not specified no assertion criteria provided clinical testing

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