ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.510G>A (p.Thr170=) (rs757544615)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164021 SCV000214626 likely benign Hereditary cancer-predisposing syndrome 2014-12-26 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Invitae RCV000230968 SCV000285200 likely benign Li-Fraumeni syndrome 2020-12-02 criteria provided, single submitter clinical testing
GeneDx RCV000429905 SCV000518405 benign not specified 2015-09-08 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Health, Inc RCV000164021 SCV000537447 likely benign Hereditary cancer-predisposing syndrome 2015-11-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000429905 SCV000918347 likely benign not specified 2018-05-01 criteria provided, single submitter clinical testing Variant summary: TP53 c.510G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. In one recent study authors predicted that the variant might affect transcription factor binding sites (Yang 2017). However, these predictions have yet to be confirmed by functional studies. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 11 fold above the estimated maximal expected allele frequency for a pathogenic variant in TP53 causing Hereditary Breast and Ovarian Cancer phenotype (4.7e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. The variant, c.510G>A, has been reported in the literature as a germline variant in individuals affected with triple negative breast cancer (Yang 2017), and it was also found in several tumor samples (of different tissue origin) as a somatic variant. These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000429905 SCV001469321 benign not specified 2020-02-06 criteria provided, single submitter clinical testing

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