ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5917A>C (p.Asn1973His) (rs1555284460)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000587760 SCV000694917 uncertain significance not provided 2016-01-29 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5917A>C variant affects a non-conserved nucleotide, resulting in amino acid change from Asn to His. 3/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). This variant is not found in 120830 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; 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 was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000791674 SCV000930933 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-24 criteria provided, single submitter clinical testing This sequence change replaces asparagine with histidine at codon 1973 of the BRCA2 protein (p.Asn1973His). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and histidine. 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 disease. ClinVar contains an entry for this variant (Variation ID: 495476). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The histidine 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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