ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.6G>A (p.Glu2=) (rs143458271)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162663 SCV000213104 likely benign Hereditary cancer-predisposing syndrome 2014-09-12 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 RCV000197468 SCV000253316 likely benign Li-Fraumeni syndrome 2020-11-26 criteria provided, single submitter clinical testing
Counsyl RCV000411973 SCV000488031 likely benign Li-Fraumeni syndrome 1 2015-12-14 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508330 SCV000602276 benign not specified 2017-03-30 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162663 SCV000686763 likely benign Hereditary cancer-predisposing syndrome 2016-07-18 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001171920 SCV001334823 likely benign not provided 2020-02-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000508330 SCV001338226 likely benign not specified 2020-02-28 criteria provided, single submitter clinical testing Variant summary: TP53 c.6G>A alters a non-conserved nucleotide resulting in a synonymous change. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 9.2e-05 in 250540 control chromosomes (gnomAD). The observed variant frequency is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in TP53 causing Li-Fraumeni Syndrome phenotype (4e-05), strongly suggesting that the variant is benign. c.6G>A has been reported in the literature (Sagne_2014). These report(s) do not provide unequivocal conclusions about association of the variant with Li-Fraumeni Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submitters (evaluation after 2014) cite the variant as likely benign/ benign. Based on the evidence outlined above, the variant was classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286538 SCV001473132 likely benign none provided 2019-11-03 criteria provided, single submitter clinical testing

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