Total submissions: 15
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000991146 | SCV001142553 | benign | Li-Fraumeni syndrome | 2019-08-28 | reviewed by expert panel | curation | This variant has a minor allele frequency of 0.001122 (0.11%, 28/24,948 alleles) in the African subpopulation of the gnomAD cohort (BA1). The variant also has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). Additionally, transactivation assays show partially functional variant 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_Supporting; PMID: 12826609, 30224644). Finally, this variant has been observed in at least 7 60+ year old females without a cancer diagnosis (BS2_Supporting; FLOSSIES database - https://whi.color.com). In summary, TP53 c.319T>C; p.Tyr107His meets criteria to be classified as benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BA1, BP4, BS3_Supporting, BS2_Supporting. |
Ambry Genetics | RCV000128936 | SCV000172807 | likely benign | Hereditary cancer-predisposing syndrome | 2019-02-16 | 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. |
Gene |
RCV000588191 | SCV000211739 | likely benign | not provided | 2021-02-23 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 15073856, 24729566, 21373875, 26580448, 26206375, 27626311, 24797764, 28056804, 25896519, 28861920, 29979965, 30352134, 33300245) |
Invitae | RCV000991146 | SCV000285186 | likely benign | Li-Fraumeni syndrome | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000411273 | SCV000489333 | uncertain significance | Li-Fraumeni syndrome 1 | 2016-09-22 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000235219 | SCV000597523 | likely benign | not specified | 2018-04-24 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000588191 | SCV000602266 | likely benign | not provided | 2022-12-02 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000235219 | SCV000697439 | benign | not specified | 2020-07-30 | criteria provided, single submitter | clinical testing | Variant summary: TP53 c.319T>C (p.Tyr107His) results in a conservative amino acid change located in the p53, DNA-binding domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. Functional studies based on the overall transcriptional activity in yeast assays classified this variant as partially functional (Kato_2003). The variant allele was found at a frequency of 0.00012 in 282734 control chromosomes, predominantly at a frequency of 0.0011 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 28 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 a benign polymorphism found primarily in populations of African or African-American origin. In addition, this variant was observed in old females, older than age 70 years who have never had cancer (FLOSSIES database). This variant has been reported in cancer patients without strong evidence for causality. Eight ClinVar submitters, including one expert panel (ClinGen TP53 Variant Curation Expert Panel, benign), (evaluation after 2014) cite the variant as uncertain significance (1x), likely benign (6x) and benign (1x). Based on the evidence outlined above, the variant was classified as benign. |
Color Diagnostics, |
RCV000128936 | SCV000910800 | likely benign | Hereditary cancer-predisposing syndrome | 2020-05-20 | criteria provided, single submitter | clinical testing | |
St. |
RCV000991146 | SCV001439183 | benign | Li-Fraumeni syndrome | 2020-09-03 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000128936 | SCV002530446 | benign | Hereditary cancer-predisposing syndrome | 2021-06-08 | criteria provided, single submitter | curation | |
Fulgent Genetics, |
RCV002498638 | SCV002810023 | likely benign | Adrenocortical carcinoma, hereditary; Familial cancer of breast; Glioma susceptibility 1; Bone osteosarcoma; Li-Fraumeni syndrome 1; Nasopharyngeal carcinoma; Carcinoma of pancreas; Choroid plexus papilloma; Basal cell carcinoma, susceptibility to, 7; Hepatocellular carcinoma; Colorectal cancer; Bone marrow failure syndrome 5 | 2022-04-16 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000411273 | SCV004017832 | uncertain significance | Li-Fraumeni syndrome 1 | 2023-04-11 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
CHEO Genetics Diagnostic Laboratory, |
RCV003492581 | SCV004239784 | benign | Breast and/or ovarian cancer | 2023-04-25 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003917413 | SCV004734797 | likely benign | TP53-related condition | 2020-03-27 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |