ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.556G>A (p.Asp186Asn)

gnomAD frequency: 0.00001  dbSNP: rs1060501206
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen TP53 Variant Curation Expert Panel, ClinGen RCV001724013 SCV001949912 likely benign Li-Fraumeni syndrome 1 2021-03-25 reviewed by expert panel curation Transactivation assays show retained function according to Kato, et al. and there is no evidence of a dominant negative effect or loss of function according to Giacomelli, et al. (BS3; PMID: 12826609, 30224644). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). In summary, TP53 c.556G>A (p.Asp186Asn) meets criteria to be classified as likely benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BS3, BP4.
Invitae RCV000467183 SCV000545352 uncertain significance Li-Fraumeni syndrome 2023-11-08 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 186 of the TP53 protein (p.Asp186Asn). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 406601). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is not expected to disrupt TP53 function with a negative predictive value of 97.5%. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609, 29979965, 30224644). 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.
GeneDx RCV000481372 SCV000566478 likely benign not provided 2019-09-10 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 17903248, 21232794, 29979965, 30224644, 30287823, 17417775, 30840781)
Ambry Genetics RCV000571882 SCV000664581 likely benign Hereditary cancer-predisposing syndrome 2020-06-11 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000481372 SCV002046459 uncertain significance not provided 2020-12-03 criteria provided, single submitter clinical testing

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.