rs180177035
Variant summary
Our verdict is Pathogenic. Variant got 17 ACMG points: 17P and 0B. PM1PM5PP2PP3_StrongPP5_Very_Strong
The NM_001374258.1(BRAF):c.770A>G(p.Gln257Arg) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q257K) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
BRAF
NM_001374258.1 missense
NM_001374258.1 missense
Scores
9
3
1
Clinical Significance
Conservation
PhyloP100: 7.97
Genes affected
BRAF (HGNC:1097): (B-Raf proto-oncogene, serine/threonine kinase) This gene encodes a protein belonging to the RAF family of serine/threonine protein kinases. This protein plays a role in regulating the MAP kinase/ERK signaling pathway, which affects cell division, differentiation, and secretion. Mutations in this gene, most commonly the V600E mutation, are the most frequently identified cancer-causing mutations in melanoma, and have been identified in various other cancers as well, including non-Hodgkin lymphoma, colorectal cancer, thyroid carcinoma, non-small cell lung carcinoma, hairy cell leukemia and adenocarcinoma of lung. Mutations in this gene are also associated with cardiofaciocutaneous, Noonan, and Costello syndromes, which exhibit overlapping phenotypes. A pseudogene of this gene has been identified on the X chromosome. [provided by RefSeq, Aug 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 17 ACMG points.
PM1
?
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 1 uncertain in NM_001374258.1
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr7-140801503-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 40351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
PP2
?
Missense variant where missense usually causes diseases, BRAF
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.963
PP5
?
Variant 7-140801502-T-C is Pathogenic according to our data. Variant chr7-140801502-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 13973.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr7-140801502-T-C is described in Lovd as [Pathogenic]. Variant chr7-140801502-T-C is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| BRAF | NM_001374258.1 | c.770A>G | p.Gln257Arg | missense_variant | 6/20 | ENST00000644969.2 | |
| BRAF | NM_004333.6 | c.770A>G | p.Gln257Arg | missense_variant | 6/18 | ENST00000646891.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BRAF | ENST00000644969.2 | c.770A>G | p.Gln257Arg | missense_variant | 6/20 | NM_001374258.1 | |||
| BRAF | ENST00000646891.2 | c.770A>G | p.Gln257Arg | missense_variant | 6/18 | NM_004333.6 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1AN: 1461672Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727140
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1461672
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727140
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:29Other:2
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
not provided Pathogenic:7
| Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 26, 2013 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 19, 2022 | The BRAF c.770A>G, p.Gln257Arg variant (rs180177035) has been reported in multiple patients diagnosed with LEOPARD syndrome, cardio-facial-cutaneous syndrome or other RASopathies (Niihori 2006, Rodriguez-Viciana 2006, Gripp 2007, Narumi 2007, Nystrom 2008, Neumann 2009, Sarkozy 2009, Carcavilla 2013, Wong Ramsey 2014). The variant is located in the cysteine-rich domain of the BRAF conserved region 1 (Niihori 2006, Rodriguez-Viciana 2006), and several additional variants in neighboring codons have also been identified in cardio-facial-cutaneous syndrome (Kiel 2014). Functional analyses of the p.Gln257Arg variant protein indicates over-activation of phospho-MEK and phospho-ERK (Rodriguez-Viciana 2006, Rodriguez-Viciana 2008) and downstream transcriptional activity (Niihori 2006), consistent with the established disease mechanisms of BRAF-related disorders. This variant is reported in ClinVar (Variation ID: 13973) and is also absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The glutamine at codon 257 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.838). Based on available information, this variant is considered to be pathogenic. References: Carcavilla A et al. LEOPARD syndrome: a variant of Noonan syndrome strongly associated with hypertrophic cardiomyopathy. Rev Esp Cardiol (Engl Ed). 2013 May;66(5):350-6. PMID: 24775816. Gripp KW et al. Further delineation of the phenotype resulting from BRAF or MEK1 germline mutations helps differentiate cardio-facio-cutaneous syndrome from Costello syndrome. Am J Med Genet A. 2007 Jul 1;143A(13):1472-80. PMID: 17551924.. Kiel C et al. Structure-energy-based predictions and network modelling of RASopathy and cancer missense mutations. Mol Syst Biol. 2014 May 6;10(5):727. PMID: 24803665. Narumi Y et al. Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome. Am J Med Genet A. 2007 Apr 15;143A(8):799-807. PMID: 17366577. Niihori T et al. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat Genet. 2006 Mar;38(3):294-6. PMID: 16474404. Nystrom AM et al. Noonan and cardio-facio-cutaneous syndromes: two clinically and genetically overlapping disorders. J Med Genet. 2008 Aug;45(8):500-6. PMID: 18456719. Rodriguez-Viciana P et al. Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. Science. 2006 Mar 3;311(5765):1287-90. PMID: 16439621. Rodriguez-Viciana P et al. Biochemical characterization of novel germline BRAF and MEK mutations in cardio-facio-cutaneous syndrome. Methods Enzymol. 2008;438:277-89. PMID: 18413255. Sarkozy A et al. Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. Hum Mutat. 2009 Apr;30(4):695-702. PMID: 19206169. - |
| Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jun 17, 2022 | Functional in vitro studies have demonstrated that the p.(Q257R) variant results in increased kinase activity and activation of downstream effectors (MEK and ERK) (Rodriguez-Viciana et al., 2008), and in vivo studies have demostrated developmental defects and CFC-like features in animal models (Anastasaki et al., 2009; Moriya et al., 2015); Missense variants in this gene are often considered pathogenic (HGMD); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17551924, 29778030, 29704308, 34573299, 17703371, 23312806, 16474404, 18042262, 19376813, 26472072, 26242988, 28809097, 27799561, 28650561, 29084544, 23340054, 30050098, 32005694, 32369273, 29907801, 33482860, 31130284, 27322245, 24719372, 24803665, 24775816, 33795686, 33040082, 33726816, 31785789, 33860439, 18413255, 29493581, 17603483, 15520807, 16439621, 15488754, 24957944) - |
| Pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Sep 21, 2018 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Clinical Genetics and Genomics, Karolinska University Hospital | Aug 22, 2017 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2020 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Molecular Diagnostics Lab, Nemours Children's Health, Delaware | Jul 23, 2015 | - - |
Cardiofaciocutaneous syndrome 1 Pathogenic:5
| Pathogenic, criteria provided, single submitter | clinical testing | Courtagen Diagnostics Laboratory, Courtagen Life Sciences | Jan 21, 2015 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn | - | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 26, 2024 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
| Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2006 | - - |
Cardio-facio-cutaneous syndrome Pathogenic:3Other:2
| Pathogenic, reviewed by expert panel | curation | ClinGen RASopathy Variant Curation Expert Panel | Apr 03, 2017 | The c.770A>G (p.Gln257Arg) variant in BRAF has been reported in the literature as a confirmed de novo occurrence in at least 2 patients with clinical features of a RASopathy (PS2_VeryStrong; PMID:18042262, PMID:17551924, PMID:16474404). In vitro functional studies provide some evidence that the p.Q257R variant may impact protein function (PS3; PMID:18413255; PMID:19376813). This variant was absent from large population studies (PM2; ExAC, http://exac.broadinstitute.org). The variant is located in the BRAF gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; PMID:29493581). Furthermore, this variant is located in exon 6, which has been defined by the ClinGen RASopathy Expert Panel to be a mutational hotspot or domain of BRAF (PM1; PMID:29493581). Computational prediction tools and conservation analysis suggest that the p.Q257R variant may impact the protein (PP3). In summary, this variant meets criteria to be classified as pathogenic for cardio-facio-cutaneous syndrome in an autosomal dominant manner. Rasopathy-specific ACMG/AMP criteria applied (PMID:29493581): PP2, PP3, PM1, PM2, PS3, PS2_VeryStrong. - |
| Pathogenic, no assertion criteria provided | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 01, 2015 | The p.Gln257Arg variant in BRAF is an established pathogenic variant for Cardiof aciocutaneous syndrome (CFC) and is absent from large population studies. The p. Gln257Arg variant is one of the most commonly identified variants in BRAF and ha s been reported in >30 individuals with CFC syndrome (Rodriguez-Viciana 2008, Sa rkozy 2009, Neumann 2009, Abe 2012 Luk 2013, Wong Ramsey 2014, LMM unpublished d ata) and in 1 individual with LEOPARD syndrome (Carcavilla 2013). De novo occurr ences have been described for several individuals (Gripp 2007, Sarkozy 2009, Luk 2013, Neumann 2009, Niihori 2006). In addition, in vitro and in vivo functional studies support that this variant impacts protein function (Anastaski 2009, Ana stasaki 2012, Wen 2013, Inoue 2014). In summary, this variant meets our criteria to be classified as pathogenic for CFC syndrome in an autosomal dominant manner based upon de novo occurrence, absence from controls, and functional evidence. - |
| not provided, no classification provided | phenotyping only | GenomeConnect - CFC International | - | Variant identified in multiple registry participants. Variant interpreted as Pathogenic and reported, most recently on 04-27-2016 by lab or GTR ID GeneDx. Variant interpreted as Pathogenic and reported on 09-25-2012 by lab or GTR ID Central Manchester University Hospitals Regional Genetics Laboratory Services. Variant interpreted as Pathogenic and reported on 04-30-2009 by lab or GTR ID Prevention Genetics. GenomeConnect - CFC International assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
| not provided, no classification provided | literature only | GeneReviews | - | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 17, 2017 | Variant summary: The BRAF c.770A>G (p.Gln257Arg) variant involves the alteration of a conserved nucleotide, is predicted to be damaging by 3/4 in silico tools (SNPs&GO not captured due to low reliability index) and is located in acylglycerol/phorbol-ester binding domain of the protein (InterPro). This variant is absent from 118580 control chromosomes from ExAC dataset. The variant is widely accepted to be pathogenic in the literature with concordant clinical and functional data. It is frequently reported in patients with CFC including evidence of de novo occurrences. In vitro as well as in vivo functional evidences are consistent with pathogenic outcome. Several clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as Pathogenic. - |
Noonan syndrome 7 Pathogenic:4
| Pathogenic, no assertion criteria provided | clinical testing | Center for Molecular Medicine, Children’s Hospital of Fudan University | Feb 08, 2022 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Jul 22, 2020 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Mar 21, 2022 | ACMG classification criteria: PS2 strong, PS3 supporting, PS4 strong, PM1 moderated, PM2 moderated, PP1 supporting, PP3 supporting - |
| Pathogenic, criteria provided, single submitter | clinical testing | Clinical Genetics Laboratory, Skane University Hospital Lund | Jun 16, 2023 | ACMG criteria used: PS3, PS4, PM2 - |
Noonan syndrome 1 Pathogenic:3
| Pathogenic, criteria provided, single submitter | clinical testing | DASA | Jan 05, 2022 | The c.770A>G;p.(Gln257Arg) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 13973; OMIM: 164757.0013; PMID:18042262; 17551924; 16474404; 17703371; 24719372; 24775816) - PS4. Well-established in vitro or in vivo functional studies support a damaging effect on the gene or gene product (PMID:18413255; 19376813; 16474404) - PS3_moderate. The variant is located in a mutational hot spot and/or critical and well-established functional domain (C1_1; PMID: 29493581) - PM1. This variant is not present in population databases (rs180177035, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. Pathogenic missense variant in this residue have been reported (ClinVar ID: 40351) - PM5. The variant was assumed de novo, but without confirmation of paternity and maternity (PMID:18042262; 17551924) - PM6_strong. Missense variant in BRAF that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease - PP2. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic. - |
| Pathogenic, no assertion criteria provided | research | Division of Human Genetics, National Health Laboratory Service/University of the Witwatersrand | - | - - |
| Pathogenic, no assertion criteria provided | clinical testing | Molecular Genetics, Centre for Human Genetics | - | - - |
RASopathy Pathogenic:2
| Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 11, 2013 | This variant has been previously reported as disease-causing and was found once in our laboratory as a de novo change in a 24-year-old female with intellectual disability, epilepsy, coarse facial features, short stature, microcephaly, and severe brain ischemia and hemiparesis following cardiac arrest at age 8y. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2023 | Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is expected to disrupt BRAF function. ClinVar contains an entry for this variant (Variation ID: 13973). This missense change has been observed in individuals with Noonan spectrum disorders (PMID: 16474404, 17703371, 24719372, 24775816). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 257 of the BRAF protein (p.Gln257Arg). Experimental studies have shown that this missense change affects BRAF function (PMID: 16474404, 18413255). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. - |
Noonan syndrome 7;C3150971:LEOPARD syndrome 3;CN029449:Cardiofaciocutaneous syndrome 1 Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Aug 13, 2019 | BRAF NM_004333.4 exon 6 p.Gln257Arg (c.770A>G): This variant is considered to be a common disease variant and has been reported in the literature in several individuals with cardiofaciocutaneous syndrome (CFC) and other Noonan-spectrum disorders, including several de novo occurrences (Niihori 2006 PMID:16474404, Gripp 2007 PMID:17551924, Schulz 2008 PMID:18042262, Sarkozy 2009 PMID:19206169, Neumann 2009 PMID:18854871, Carcavilla 2013 PMID:24775816, Wong Ramsey 2014 PMID:24719372, Joyce 2016 PMID:26242988, Xu 2017 PMID:29084544). This variant is not present in large control databases but is present in ClinVar, with several labs classifying this variant as pathogenic, including an entry from the ClinGen RASopathies Expert Panel (Variation ID:13973). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In addition, both in vitro and in vivo functional studies support that this variant will impact the protein (Niihori 2006 PMID:16474404, Rodriguez-Viciana 2008 PMID:18403255, Anastasaki 2009 PMID:19376813, Inoue 2014 PMID:25035421). In summary, this variant is classified as pathogenic based on the data above. - |
LEOPARD syndrome 3 Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 02, 2019 | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Lung cancer;C0346629:Colorectal cancer;C1835047:Melanoma, cutaneous malignant, susceptibility to, 1;C3150970:Noonan syndrome 7;C3150971:LEOPARD syndrome 3;CN029449:Cardiofaciocutaneous syndrome 1 Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | BRAF NM_004333.4 exon 6 p.Gln257Arg (c.770A>G): This variant is considered to be a common disease variant and has been reported in the literature in several individuals with cardiofaciocutaneous syndrome (CFC) and other Noonan-spectrum disorders, including several de novo occurrences (Niihori 2006 PMID:16474404, Gripp 2007 PMID:17551924, Schulz 2008 PMID:18042262, Sarkozy 2009 PMID:19206169, Neumann 2009 PMID:18854871, Carcavilla 2013 PMID:24775816, Wong Ramsey 2014 PMID:24719372, Joyce 2016 PMID:26242988, Xu 2017 PMID:29084544). This variant is not present in large control databases but is present in ClinVar, with several labs classifying this variant as pathogenic, including an entry from the ClinGen RASopathies Expert Panel (Variation ID:13973). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In addition, both in vitro and in vivo functional studies support that this variant will impact the protein (Niihori 2006 PMID:16474404, Rodriguez-Viciana 2008 PMID:18403255, Anastasaki 2009 PMID:19376813, Inoue 2014 PMID:25035421). In summary, this variant is classified as pathogenic based on the data above. - |
Cardiovascular phenotype Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 05, 2024 | The p.Q257R pathogenic mutation (also known as c.770A>G), located in coding exon 6 of the BRAF gene, results from an A to G substitution at nucleotide position 770. The glutamine at codon 257 is replaced by arginine, an amino acid with highly similar properties. This variant has been reported in multiple individuals with features consistent with BRAF-related RASopathy, including several de novo occurrences (Niihori T et al. Nat Genet, 2006 Mar;38:294-6; Gripp KW et al. Am J Med Genet A, 2007 Jul;143A:1472-80; Wong Ramsey KN et al. Am J Med Genet A, 2014 Aug;164A:2036-42; Joyce S et al. Eur J Hum Genet, 2016 May;24:690-6; Mucciolo M et al. Int J Mol Sci, 2016 Jun;17; Mellis R et al. BJOG, 2022 Jan;129:52-61). In an assay testing BRAF function, this variant showed a functionally abnormal result (Rodriguez-Viciana P et al. Methods Enzymol, 2008;438:277-89). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. - |
Noonan syndrome and Noonan-related syndrome Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Apr 01, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
A
PrimateAI
Pathogenic
D
Polyphen
0.96
.;.;D;.
Vest4
0.92
MutPred
Gain of MoRF binding (P = 0.0136);Gain of MoRF binding (P = 0.0136);Gain of MoRF binding (P = 0.0136);Gain of MoRF binding (P = 0.0136);
MVP
0.99
MPC
1.3
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at