ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1504A>C (p.Lys502Gln) (rs276174809)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223354 SCV000276062 likely benign Hereditary cancer-predisposing syndrome 2015-06-01 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000112928 SCV000145879 benign Breast-ovarian cancer, familial 2 2010-12-17 no assertion criteria provided clinical testing
Color RCV000223354 SCV000911441 benign Hereditary cancer-predisposing syndrome 2016-10-06 criteria provided, single submitter clinical testing
GeneDx RCV000160038 SCV000210271 uncertain significance not provided 2014-07-26 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.1504A>C at the cDNA level, p.Lys502Gln (K502Q) at the protein level, and results in the change of a Lysine to a Glutamine (AAA>CAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Lys502Gln was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Lysine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Lys502Gln occurs at a position that is moderately conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA2 Lys502Gln is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000637723 SCV000759196 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-31 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamine at codon 502 of the BRCA2 protein (p.Lys502Gln). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with breast cancer (PMID: 26997744, 10923033). However, in one of these individuals a pathogenic allele was also identified in BRCA1, which suggests that this c.1504A>C variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 125946). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly 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 RCV000637723 SCV000838758 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing

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