ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3635A>T (p.Asn1212Ile) (rs80358609)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044232 SCV000072245 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-06-12 criteria provided, single submitter clinical testing This sequence change replaces asparagine with isoleucine at codon 1212 of the BRCA2 protein (p.Asn1212Ile). The asparagine residue is weakly conserved and there is a large physicochemical difference between asparagine and isoleucine. This variant is present in population databases (rs80358609, ExAC 0.009%). This variant has been reported in an individual in the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 51495). 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: "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.
Ambry Genetics RCV000166119 SCV000216889 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000588318 SCV000694708 uncertain significance not provided 2017-03-07 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.3635A>T (p.Asn1212Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 4/5 in silico tools predict a damaging outcome for this variant. This variant was found in 1/120932 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). Multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
PreventionGenetics,PreventionGenetics RCV000588318 SCV000805697 uncertain significance not provided 2017-10-26 criteria provided, single submitter clinical testing
Color RCV000166119 SCV000906901 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-31 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588318 SCV001133766 uncertain significance not provided 2019-03-26 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113199 SCV000146268 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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