ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.956A>G (p.Asn319Ser) (rs55939572)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000128972 SCV000172857 benign Hereditary cancer-predisposing syndrome 2015-01-15 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000083161 SCV000145793 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000128972 SCV000902830 benign Hereditary cancer-predisposing syndrome 2016-01-05 criteria provided, single submitter clinical testing
Counsyl RCV000083161 SCV000487870 uncertain significance Breast-ovarian cancer, familial 2 2015-11-24 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000045856 SCV000591721 uncertain significance not specified 2013-01-08 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000045856 SCV000588074 uncertain significance not specified 2017-04-20 criteria provided, single submitter clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735630 SCV000863768 uncertain significance Breast and/or ovarian cancer 2012-10-18 no assertion criteria provided clinical testing
GeneDx RCV000045856 SCV000210553 likely benign not specified 2017-08-07 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000587951 SCV000695252 uncertain significance not provided 2017-03-02 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.956A>G (p.Asn319Ser) variant involves the missense alteration of a non-conserved nucleotide. 3/5 in silico tools predict a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may create an SC35 ESE site. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control population database ExAC at a frequency of 0.0000333 (4/120200 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). Multiple clinical diagnostic laboratories/reputable databases have conflicting classifications for this variant, including benign (1x), likely benign (2x), and uncertain significance (4x). Several publications cite the variant in affected individuals but do not provide co-segregation or co-occurrence data. Taken together, this variant is classified as VUS until additional information becomes available.
Invitae RCV000195386 SCV000073869 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-04-27 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 319 of the BRCA2 protein (p.Asn319Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs55939572, ExAC 0.006%). This variant has been reported in an individual affected with breast and pancreatic cancer (PMID: 20104584, 25479140). ClinVar contains an entry for this variant (Variation ID: 52869). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Sharing Clinical Reports Project (SCRP) RCV000083161 SCV000115235 likely benign Breast-ovarian cancer, familial 2 2009-02-13 no assertion criteria provided clinical testing

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