ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1315T>G (p.Phe439Val) (rs80358420)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757039 SCV000885090 uncertain significance not provided 2017-10-18 criteria provided, single submitter clinical testing The BRCA2 c.1315T>G; p.Phe439Val variant is not described in the medical literature or in gene-specific databases. The variant is listed in the ClinVar database (Variation ID: 51100), in the dbSNP variant database (rs80358420) and in the Genome Aggregation Database in 1/30962 alleles. The phenylalanine at this position is weakly conserved across species and computational algorithms (AlignGVGD, PolyPhen2, SIFT) predict this variant is tolerated. Considering available information, there is insufficient evidence to classify this variant with certainty.
Ambry Genetics RCV000162696 SCV000213151 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Breast Cancer Information Core (BIC) (BRCA2) RCV000112907 SCV000145852 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000162696 SCV000906885 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-06 criteria provided, single submitter clinical testing
Counsyl RCV000112907 SCV000785918 uncertain significance Breast-ovarian cancer, familial 2 2018-01-10 criteria provided, single submitter clinical testing
Invitae RCV000043780 SCV000071793 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-05-04 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with valine at codon 439 of the BRCA2 protein (p.Phe439Val). The phenylalanine residue is weakly conserved and there is a small physicochemical difference between phenylalanine and valine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA2-related disease. This variant has been observed in an individual in the Breast Cancer Information Core database (PMID: 10923033). However, in that individual a pathogenic allele was also identified in BRCA1, which suggests that this c.1315T>G variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 51100). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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