ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2843T>C (p.Val948Ala) (rs730881517)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000542950 SCV000635250 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-03-20 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 948 of the BRCA2 protein (p.Val948Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine. 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: 182192). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine 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.
Ambry Genetics RCV000570238 SCV000668840 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Counsyl RCV000662673 SCV000785378 uncertain significance Breast-ovarian cancer, familial 2 2017-07-18 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781051 SCV000918836 uncertain significance not specified 2017-10-26 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.2843T>C (p.Val948Ala) variant involves the alteration of a non-conserved nucleotide. 3/5 in silico tools predict a damaging outcome for this variant. This variant is absent in 245522 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases; 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.

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