ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.425G>A (p.Ser142Asn) (rs397507713)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000509645 SCV000607814 likely pathogenic Hereditary cancer-predisposing syndrome 2017-05-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Last nucleotide of exon,Well-characterized mutation at same position,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000258256 SCV000326997 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727660 SCV000854964 likely pathogenic not provided 2016-02-17 criteria provided, single submitter clinical testing
Invitae RCV000548158 SCV000635354 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-25 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 142 of the BRCA2 protein (p.Ser142Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. This variant also falls at the last nucleotide of exon 4 of the BRCA2 coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs397507713, ExAC 0.03%). This variant has been reported in an affected individual in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 197099). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of nucleotide changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.