17-7675088-C-T
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2_SupportingPP3PS4_ModeratePS3PP1_Moderate
This summary comes from the ClinGen Evidence Repository: The NM_000546.6: c.524G>A variant in TP53 is a missense variant predicted to cause substitution of arginine by histidine at amino acid 175 (p.Arg175His). This variant has been reported in 3 unrelated families meeting Classic and Revised Chompret criteria.Based on this evidence, this variant scores 2.5 total points meeting the TP53 VCEP phenotype scoring criteria of 2-3.5 points. (PS4_Moderate: 8825920, 11370630, 8164043). The variant has been reported to segregate with LFS-associated cancers in 5-6 meioses in 1 family (PP1_Moderate; PMID:8825920). In vitro assays performed in yeast and/or human cell lines showed non-functional transactivation and loss of growth suppression activity indicating that this variant impacts protein function (PS3; PMIDs: 12826609, 30224644, 29979965). This variant resides within a codon (NM_00546.4: 175, 245, 248, 249, 273, 282) of TP53 that is defined as a mutational hotspot by the ClinGen TP53 VCEP (PM1; PMID:8023157). Computational predictor scores (BayesDel = 0.54619; Align GVGD = Class C25) are above recommended thresholds (BayesDel > 0.16 and an Align GVGD Class of > 15), evidence that correlates with impact to TP53 via protein change (PP3). This variant has an allele frequency of 0.000005932 (7/1180032 alleles) in the European (non-Finnish) population in gnomAD v4.1.0 which is lower than the Clingen TP53 VCEP threshold (<0.00004) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). In summary, this variant meets the criteria to be classified as [CLASSIFICATION] for Li Fraumeni syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen TP53 VCEP: PS3, PP1_Moderate, PM1, PS4_Moderate, PP3, PM2_Supporting. (Bayesian Points: 12; VCEP specifications version 2.0; 9/6/2024) LINK:https://erepo.genome.network/evrepo/ui/classification/CA000251/MONDO:0018875/009
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
TP53
NM_000546.6 missense
NM_000546.6 missense
Scores
15
2
2
Clinical Significance
Conservation
PhyloP100: 6.16
Genes affected
TP53 (HGNC:11998): (tumor protein p53) This gene encodes a tumor suppressor protein containing transcriptional activation, DNA binding, and oligomerization domains. The encoded protein responds to diverse cellular stresses to regulate expression of target genes, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. Mutations in this gene are associated with a variety of human cancers, including hereditary cancers such as Li-Fraumeni syndrome. Alternative splicing of this gene and the use of alternate promoters result in multiple transcript variants and isoforms. Additional isoforms have also been shown to result from the use of alternate translation initiation codons from identical transcript variants (PMIDs: 12032546, 20937277). [provided by RefSeq, Dec 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PS3
For more information check the summary or visit ClinGen Evidence Repository.
PS4
For more information check the summary or visit ClinGen Evidence Repository.
PM1
For more information check the summary or visit ClinGen Evidence Repository.
PM2
For more information check the summary or visit ClinGen Evidence Repository.
PP1
For more information check the summary or visit ClinGen Evidence Repository.
PP3
For more information check the summary or visit ClinGen Evidence Repository.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TP53 | NM_000546.6 | c.524G>A | p.Arg175His | missense_variant | 5/11 | ENST00000269305.9 | NP_000537.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TP53 | ENST00000269305.9 | c.524G>A | p.Arg175His | missense_variant | 5/11 | 1 | NM_000546.6 | ENSP00000269305.4 |
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GnomAD3 genomes 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 33
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:33Other:1
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Li-Fraumeni syndrome 1 Pathogenic:8
| Pathogenic, criteria provided, single submitter | research | Department of Pediatrics, Memorial Sloan Kettering Cancer Center | Dec 15, 2020 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 18, 2022 | - - |
| Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2005 | - - |
| Pathogenic, no assertion criteria provided | clinical testing | Pathway Genomics | Jul 24, 2014 | - - |
| Pathogenic, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The TP53 p.Arg175His variant was identified in 14 of 2378 proband chromosomes (frequency: 0.006) from individuals or families with Li Fraumeni syndrome, breast, ovarian and/or colon cancer (Walsh 2011, Melhem-Bertrandt 2012, Wong 2006, Bougeard 2008, Damineni 2014). This variant has also been identified in a child diagnosed with adrenocortical carcinoma at 6 months of age (Choong 2012) and a family that includes two individuals diagnosed with childhood sarcomas and four individuals diagnosed with brain tumours (Varley 1995). The variant was identified in dbSNP and ClinVar (classified as pathogenic by GeneDx, Invitae, Ambry Genetics, and 8 other submitters) . The variant was identified in control databases in 1 of 251276 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European (non-Finnish) population in 1 of 113600 chromosomes (freq: 0.000009), while the variant was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other or South Asian populations. The R175 residue is a mutation hotspot and results in a structurally unstable, unfolded p53 protein (Xu 2014). The R175H variant has been shown to confer oncogenic gain of function to the p53 protein by multiple studies (Petitjean 2007, Capponcelli 2005), which is hypothesized to occur via the increased activation of the c-Met receptor tyrosine kinase and/or the inactivation of the ATM-dependent DNA damage response, resulting in a defective G2/M checkpoint (Grugan 2013, Liu 2010). The p.Arg175 residue is conserved across mammals and other organisms and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the His variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Nov 12, 2024 | Criteria applied: PS3,PS4,PM1,PP3 - |
| Pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | May 11, 2023 | This variant is considered pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID:8825920, 8118819, 7887414]. Functional studies indicate this variant impacts protein function [PMID: 14743206, 15607980]. This variant is expected to disrupt protein structure [PMID: 8023157, Myriad internal data]. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Mar 18, 2016 | - - |
not provided Pathogenic:7
| Pathogenic, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
| Pathogenic, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jan 04, 2021 | Published functional studies demonstrate a damaging effect: non-functional transactivation, loss of growth suppression activity (Kato et al., 2003; Monti et al., 2011; Wasserman et al., 2015; Kotler et al., 2018); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31447099, 31105275, 15510160, 12826609, 19556618, 21343334, 25584008, 29979965, 8118819, 8164043, 10864200, 12200603, 16401470, 22233476, 28369373, 30577483, 30840781, 30093976, 29324801, 30092803, 30720243, 30709875, 28472496, 29753700, 29360550, 28975465, 29470806, 19127115, 29360161, 28818432, 29416795, 27153395, 12610779, 11494139, 11370630, 8308926, 7887414, 8099841, 23792586, 20689556, 15492269, 21426305, 22006311, 24573247, 22286061, 21305319, 17606709, 21761402, 24651015, 20128691, 24729566, 15170137, 29489754, 28861920, 28724667, 15607981, 15607980, 27516001, 27374712, 27714481, 27501770, 27323394, 23172776, 22265402, 21601526, 22851211, 21059199, 20501846, 18511570, 17308077, 16551709, 15951970) - |
| Pathogenic, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
| Pathogenic, no assertion criteria provided | clinical testing | Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute | - | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 17, 2017 | - - |
| Pathogenic, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | - | - - |
Li-Fraumeni syndrome Pathogenic:5
| Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 175 of the TP53 protein (p.Arg175His). This variant is present in population databases (rs28934578, gnomAD 0.0009%). This missense change has been observed in individual(s) with Li-Fraumeni syndrome (PMID: 8164043, 8825920, 16401470, 21761402, 22006311). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 12374). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function with a positive predictive value of 97.5%. Experimental studies have shown that this missense change affects TP53 function (PMID: 12007217, 12826609, 15607980, 15607981, 20516128, 23263379, 24573247, 29979965, 30224644). For these reasons, this variant has been classified as Pathogenic. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 07, 2022 | Variant summary: TP53 c.524G>A (p.Arg175His) results in a non-conservative amino acid change located in the p53, DNA-binding domain (IPR011615) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251276 control chromosomes. c.524G>A has been reported in the literature in multiple individuals affected with Li-Fraumeni Syndrome, including 2 families where the variant strongly segregated with disease (Varley_1995, Varley_1997, etc). These data indicate that the variant is very likely to be associated with disease. In vitro functional studies show that R175H results in decreased activation of Tp53 targets, and additionally confers a gain of function to Tp53, resulting in aberrant activation of gene transcription and enhanced cell migration (TP53 database, Yeudall_2012). Additional evidence from an animal model indicates that this variant contributes to a phenotype similar to tumorigenesis (including thymic tumors, sarcomas, peripheral lymphomas and germ-cell tumors) (Liu_2010). Ten ClinVar submitters have assessed this variant since 2014: all ten classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 24, 2017 | The p.Arg175His variant in TP53 has been reported in >16 individuals with Li-Fra umeni syndrome, and segregated with disease in 3 affected relatives from 1 famil y (McIntyre 1994, Varley 1997, Wong 2006, Bougeard 2008, Walsh 2011, Melhem-Bert randt 2012, Park 2016). This variant has also been reported by another clinical laboratory in ClinVar (Variation ID# 12374). In vitro functional studies provide some evidence that the p.Arg175His variant may impact protein function (Kogan-S akin 2011, Grugan 2013) and an in-vivo mouse model has shown that this variant c auses TP53-related tumors (Liu 2010). Additionally, the p.Arg175His variant has been identified in 1/111550 European chromosomes by gnomAD (http://gnomad.broadi nstitute.org). Computational prediction tools and conservation analysis suggest that the p.Arg175His variant may impact the protein and 3 other amino acid chang es at this position (Leu, Gly, Cys) have been associated with Li-Fraumeni syndro me (HGMD database; Stenson 2017). In summary, this variant meets criteria to be classified as pathogenic for Li-Fraumeni syndrome in an autosomal dominant manne r based on segregation studies, increased prevalence in affected individuals, ve ry low frequency in controls and functional evidence. ACMG/AMP Criteria applied: PS4, PP1, PS3, PM2. - |
| Pathogenic, reviewed by expert panel | curation | ClinGen TP53 Variant Curation Expert Panel, ClinGen | Sep 06, 2024 | The NM_000546.6: c.524G>A variant in TP53 is a missense variant predicted to cause substitution of arginine by histidine at amino acid 175 (p.Arg175His). This variant has been reported in 3 unrelated families meeting Classic and Revised Chompret criteria.Based on this evidence, this variant scores 2.5 total points meeting the TP53 VCEP phenotype scoring criteria of 2-3.5 points. (PS4_Moderate: 8825920, 11370630, 8164043). The variant has been reported to segregate with LFS-associated cancers in 5-6 meioses in 1 family (PP1_Moderate; PMID: 8825920). In vitro assays performed in yeast and/or human cell lines showed non-functional transactivation and loss of growth suppression activity indicating that this variant impacts protein function (PS3; PMIDs: 12826609, 30224644, 29979965). This variant resides within a codon (NM_00546.4: 175, 245, 248, 249, 273, 282) of TP53 that is defined as a mutational hotspot by the ClinGen TP53 VCEP (PM1; PMID: 8023157). Computational predictor scores (BayesDel = 0.54619; Align GVGD = Class C25) are above recommended thresholds (BayesDel > 0.16 and an Align GVGD Class of > 15), evidence that correlates with impact to TP53 via protein change (PP3). This variant has an allele frequency of 0.000005932 (7/1180032 alleles) in the European (non-Finnish) population in gnomAD v4.1.0 which is lower than the Clingen TP53 VCEP threshold (<0.00004) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). In summary, this variant meets the criteria to be classified as [CLASSIFICATION] for Li Fraumeni syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen TP53 VCEP: PS3, PP1_Moderate, PM1, PS4_Moderate, PP3, PM2_Supporting. (Bayesian Points: 12; VCEP specifications version 2.0; 9/6/2024) - |
| Pathogenic, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Sep 18, 2023 | This missense variant replaces arginine with histidine at codon 175 in the DNA binding domain of the TP53 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant results in the loss of TP53 protein function (PMID: 12826609, 15607981, 23263379, 29979965, 30224644), causes chromosomal instability (PMID: 25059482), and promotes tumor cell invasion (PMID: 15607981, 23792586). In mouse models of Li-Fraumeni syndrome, this variant has also been shown to impair TP53 function and cause TP53-related tumors (PMID: 15607980, 15607981). This variant has been reported in individuals affected with Li-Fraumeni syndrome meeting classic or Chompret diagnostic criteria (PMID: 8164043 , 8825920, 16401470, 21761402, 23172776, 27374712, 27516001). This variant has been shown to segregate with disease in a 4-generation extended family affected with Li-Fraumeni syndrome (PMID: 8825920). This variant has been identified in 1/251276 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. - |
Hereditary cancer-predisposing syndrome Pathogenic:3
| Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 19, 2024 | The p.R175H pathogenic mutation (also known as c.524G>A), located in coding exon 4 of the TP53 gene, results from a G to A substitution at nucleotide position 524. This changes the amino acid from an arginine to a histidine at codon 175. This mutation occurs at a well-characterized mutation hotspot (codon 175) in the critical DNA binding domain, and is associated with a classic LFS-associated tumor spectrum, including osteosarcomas, rhabdomyosarcomas, early onset colon cancer, breast cancer, and pediatric adrenal cortical tumors (McIntyre JF et al. J. Clin. Oncol. 1994 May;12(5):925-930; Varley JM et al. J. Med. Genet. 1995 Dec;32:942-945; Wong P et al. Gastroenterology. 2006 Jan;130:73-79; Hwang SM et al. Korean J. Lab Med. 2008 Dec;28(6):493-497; Melhem-Bertrandt A et al. Cancer. 2012 Feb;118(4):908-13; Choong SS et al. Clin. Genet. 2012 Dec;82(6):564-8; Maxwell KN et al. Am. J. Hum. Genet. 2016 May;98:801-17; Park KJ et al. Ann. Lab. Med. 2016 Sep;36:463-8; Dudley B et al. Cancer. 2018 Apr;124(8):1691-1700). This variant is reported to have non-functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is deficient at growth suppression and has a dominant negative effect (Kotler E et al. Mol.Cell. 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This alteration has been observed numerous times as a somatic mutation in the cancerhotspots.org database (Chang MT et al. Cancer Discov. 2018 02;8:174-183). This variant has been detected in at least one individual at an allele fraction that is suggestive of clonal hematopoiesis, a predictor of TP53 pathogenicity (Ambry internal data; Fortuno C et al. Genet Med. 2022 03;24:673-680). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 18, 2022 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jul 26, 2023 | This missense variant replaces arginine with histidine at codon 175 in the DNA binding domain of the TP53 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant results in the loss of TP53 protein function (PMID: 12826609, 15607981, 23263379, 29979965, 30224644), causes chromosomal instability (PMID: 25059482), and promotes tumor cell invasion (PMID: 15607981, 23792586). In mouse models of Li-Fraumeni syndrome, this variant has also been shown to impair TP53 function and cause TP53-related tumors (PMID: 15607980, 15607981). This variant has been reported in individuals affected with Li-Fraumeni syndrome meeting classic or Chompret diagnostic criteria (PMID: 8164043 , 8825920, 16401470, 21761402, 23172776, 27374712, 27516001). This variant has been shown to segregate with disease in a 4-generation extended family affected with Li-Fraumeni syndrome (PMID: 8825920). This variant has been identified in 1/251276 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. - |
Malignant tumor of esophagus Pathogenic:1
| Pathogenic, no assertion criteria provided | clinical testing | Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo | Jul 29, 2016 | SIFT:Deleterious (score: 0) MutationTaster:Disease causing (p-value: 1) - |
Gastric cancer Pathogenic:1
| Pathogenic, no assertion criteria provided | research | Laboratory for Genotyping Development, RIKEN | Jul 01, 2021 | - - |
Familial cancer of breast Pathogenic:1
| Pathogenic, no assertion criteria provided | clinical testing | University Health Network, Princess Margaret Cancer Centre | Mar 19, 2021 | - - |
Ovarian neoplasm Pathogenic:1
| Likely pathogenic, no assertion criteria provided | research | German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne | Dec 01, 2018 | - - |
Lip and oral cavity carcinoma Pathogenic:1
| Pathogenic, no assertion criteria provided | research | Institute of Medical Sciences, Banaras Hindu University | Apr 30, 2019 | - - |
Adrenocortical carcinoma, hereditary Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 28, 2024 | - - |
Colorectal cancer Pathogenic:1
| Pathogenic, criteria provided, single submitter | case-control | Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo | - | - - |
Choroid plexus papilloma;C0235974:Carcinoma of pancreas;C0346153:Familial cancer of breast;C0346629:Colorectal cancer;C0585442:Bone osteosarcoma;C1835398:Li-Fraumeni syndrome 1;C1859972:Adrenocortical carcinoma, hereditary;C2239176:Hepatocellular carcinoma;C2750850:Glioma susceptibility 1;C2931822:Nasopharyngeal carcinoma;C3553606:Basal cell carcinoma, susceptibility to, 7;C4748488:Bone marrow failure syndrome 5 Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 10, 2022 | - - |
TP53-related disorder Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Swedish National ChiCaP Initative, Genomic Medicine Sweden | May 01, 2024 | - - |
Squamous cell carcinoma of the head and neck Pathogenic:1
| Pathogenic, criteria provided, single submitter | case-control | Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo | - | - - |
Neoplasm Other:1
| -, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Jul 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D;D;.;.;.;.;T;T;.;D;.;.;.;.;.;.;D;.;.;.;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
D;D;D;D;D;D;D;D;.;.;.;D;D;.;D;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
.;.;.;.;.;.;.;.;.;M;.;M;M;M;.;.;M;.;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.;.;.;.;.;.;.;D;.;.;D;D;.;.;D;.;.;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;.;.;.;.;.;.;.;D;.;.;D;D;.;.;D;.;.;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.
Polyphen
D;.;.;.;.;.;.;.;.;P;.;P;D;P;.;.;P;.;.;.;D
Vest4
MutPred
Loss of stability (P = 0.0011);Loss of stability (P = 0.0011);.;.;.;.;.;.;.;Loss of stability (P = 0.0011);.;Loss of stability (P = 0.0011);Loss of stability (P = 0.0011);Loss of stability (P = 0.0011);.;.;Loss of stability (P = 0.0011);.;.;.;.;
MVP
MPC
1.1
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at