ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7992T>G (p.Ile2664Met) (rs80359800)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000566432 SCV000661272 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
Color RCV000566432 SCV000683931 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-30 criteria provided, single submitter clinical testing
Counsyl RCV000411343 SCV000488752 uncertain significance Breast-ovarian cancer, familial 2 2016-06-04 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765140 SCV000896366 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial 2; Fanconi anemia, complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer 2; Glioma susceptibility 3 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000656803 SCV000210457 uncertain significance not provided 2017-07-20 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.7992T>G at the cDNA level, p.Ile2664Met (I2664M) at the protein level, and results in the change of an Isoleucine to a Methionine (ATT>ATG). Using alternate nomenclature, this variant would be defined as BRCA2 c.8220T>G. This variant has been observed in at least one individual with either a personal or family history of breast and/or ovarian cancer (Laitman 2011). BRCA2 Ile2664Met was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Isoleucine and Methionine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Ile2664Met occurs at a position where amino acids with properties similar to Isoleucine are tolerated across species and is located in the DNA binding domain (Yang 2002). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether BRCA2 Ile2664Met is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000709332 SCV000957748 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-30 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 2664 of the BRCA2 protein (p.Ile2664Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with hereditary breast and/or ovarian cancer (PMID: 27882536, 20960228). ClinVar contains an entry for this variant (Variation ID: 182247). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV000709332 SCV000838863 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
PreventionGenetics RCV000656803 SCV000805773 uncertain significance not provided 2018-01-04 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160146 SCV000600775 uncertain significance not specified 2016-10-29 criteria provided, single submitter clinical testing

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