ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5777G>A (p.Ser1926Asn) (rs869320795)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Michigan Medical Genetics Laboratories,University of Michigan RCV000211032 SCV000267787 likely benign Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV000570052 SCV000661324 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-07 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV000570052 SCV000688948 uncertain significance Hereditary cancer-predisposing syndrome 2020-02-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589776 SCV000694901 uncertain significance not provided 2017-02-16 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5777G>A (p.Ser1926Asn) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 121042 control chromosomes. One clinical diagnostic laboratory classified this variant as likely benign, without evidence for independent evaluation. 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.
Invitae RCV001230214 SCV001402688 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-08-24 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 1926 of the BRCA2 protein (p.Ser1926Asn). The serine residue is moderately conserved and there is a small physicochemical difference between serine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 225745). 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 asparagine 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.

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