GeneBe

17-31261733-C-T

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong

The NM_001042492.3(NF1):​c.4600C>T​(p.Arg1534*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R1534R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NF1
NM_001042492.3 stop_gained

Scores

4
2

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:35

Conservation

PhyloP100: 2.12

Publications

53 publications found
Variant links:
Genes affected
NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]
NF1 Gene-Disease associations (from GenCC):
  • neurofibromatosis type 1
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Genomics England PanelApp
  • neurofibromatosis-Noonan syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia
  • Moyamoya disease
    Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
  • hereditary pheochromocytoma-paraganglioma
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • familial ovarian cancer
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 18 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-31261733-C-T is Pathogenic according to our data. Variant chr17-31261733-C-T is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 220152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042492.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
NF1
NM_001042492.3
MANE Select
c.4600C>Tp.Arg1534*
stop_gained
Exon 35 of 58NP_001035957.1
NF1
NM_000267.4
c.4537C>Tp.Arg1513*
stop_gained
Exon 34 of 57NP_000258.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
NF1
ENST00000358273.9
TSL:1 MANE Select
c.4600C>Tp.Arg1534*
stop_gained
Exon 35 of 58ENSP00000351015.4
NF1
ENST00000356175.7
TSL:1
c.4537C>Tp.Arg1513*
stop_gained
Exon 34 of 57ENSP00000348498.3
NF1
ENST00000579081.6
TSL:1
n.4537C>T
non_coding_transcript_exon
Exon 34 of 58ENSP00000462408.2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152116
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000796
AC:
2
AN:
251346
AF XY:
0.00000736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1459838
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726230
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33410
American (AMR)
AF:
0.0000224
AC:
1
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26124
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39686
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86170
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53408
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4178
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111916
Other (OTH)
AF:
0.00
AC:
0
AN:
60228
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.350
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152116
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74308
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41414
American (AMR)
AF:
0.00
AC:
0
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5196
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68014
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:35
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Neurofibromatosis, type 1 Pathogenic:20
Oct 26, 2020
Genome Diagnostics Laboratory, The Hospital for Sick Children
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This sequence change creates a premature translational stop signal (p.Arg1513*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). This variant is present in population databases (rs760703505, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with neurofibromatosis type 1 (PMID: 9180088, 10712197, 16479075, 21354044, 23668869, 26969325). ClinVar contains an entry for this variant (Variation ID: 220152). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

Jul 01, 2023
Division of Human Genetics, National Health Laboratory Service/University of the Witwatersrand
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:research

Laboratori Clínic ICS Lleida, Hospital Universitari Arnau de Vilanova
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:clinical testing

We report the c.4537C>T (p.Arg1513*) in our family study because this variant it's associated with pheochromocytoma and GIST tumor

Nov 09, 2020
Clinical Genetics Laboratory, Region Ostergotland
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

PVS1, PS4, PM6, PP5

Sep 02, 2022
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated juvenile myelomonocytic leukemia (MIM#607785), familial spinal neurofibromatosis (MIM#162210), neurofibromatosis type 1 (MIM#162200), neurofibromatosis-Noonan syndrome (MIM#601321) and Watson syndrome (MIM#193520). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Disease manifestation can be extremely variable, even within a family (GeneReviews). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2) <0.001 for a dominant condition (2 heterozygotes, 0 homozygotes). (SP) 0701 - Other null variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. At least ten NMD-predicted variants have been classified as likely pathogenic or pathogenic (DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been classified as likely pathogenic and pathogenic by multiple clinical diagnostic laboratories and has been reported in individuals with neurofibromatosis type 1 (ClinVar; PMIDs: 23668869, 27838393). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

Dec 20, 2019
Medical Genetics, University of Parma
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Apr 25, 2023
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Jul 16, 2020
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Variant summary: NF1 c.4537C>T (p.Arg1513X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251346 control chromosomes (gnomAD). The variant, c.4537C>T, had been reported as a recurring pathogenic variant in several individuals affected with Neurofibromatosis Type 1 (e.g. Side_1997, Frayling_2019, Yao_2019). Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and all of them classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

Jul 27, 2023
Clinical Genomics Laboratory, Washington University in St. Louis
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The NF1 c.4600C>T (p.Arg1534Ter) variant, also published as NF1 c.4537C>T, was identified at an allelic fraction consistent with somatic origin. This variant has been reported in numerous individuals affected with neurofibromatosis type 1 (Chai et al., PMID 31533651; Ko et al., PMID: 23668869; Yao et al., PMID 31717729; Giuliano et al, PMID 31370276). NF1 c.4600C>T (p.Arg1534Ter) has been reported in the ClinVar database as pathogenic/likely pathogenic by 22 submitters (ClinVar ID 220152). This variant is only observed on 1/152116 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant leads to a premature termination codon, which is predicted to result in nonsense mediated decay and loss of function is the known disease mechanism. Based on an internally-developed protocol informed by the ACMG/AMP guidelines (Richards S et al., PMID: 25741868) and and gene-specific practices from the ClinGen Criteria Specification Registry, the NF1 c.4600C>T (p.Arg1534Ter) variant is classified as pathogenic.

Feb 14, 2023
Neuberg Centre For Genomic Medicine, NCGM
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The stop gained c.4600C>T (p.Arg1534Ter) variant in the NF1 gene has been been reported as a recurring pathogenic variant in several individuals affected with Neurofibromatosis Type 1 (Yao et al., 2019; Ko JM et al., 2013). This variant is reported with the allele frequency 0.0007% in the gnomAD and novel in 1000 genome database. This variant has been reported to the ClinVar database as Likely Pathogenic/ Pathogenic (multiple submissions). The nucleotide change c.4600C>T in NF1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.

Nov 12, 2024
NHS Central & South Genomic Laboratory Hub
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Mar 15, 2022
Genome-Nilou Lab
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Nov 01, 2016
Center for Human Genetics, Inc, Center for Human Genetics, Inc
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Dec 16, 2024
Genetics Laboratory, UDIAT-Centre Diagnòstic, Hospital Universitari Parc Tauli
Significance:Likely pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

PVS1_very strong;PS4_supporting

Juno Genomics, Hangzhou Juno Genomics, Inc
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Absent from controls (or at extremely low frequency if recessive) in Genome Aggregation Database, Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium.;Null variant in a gene where loss of function (LOF) is a known mechanism of disease.;The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls.;Patient's phenotype or family history is highly specific for a disease with a single genetic etiology.;Assumed de novo, but without confirmation of paternity and maternity.

Apr 02, 2020
Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Jul 16, 2025
Institute of Human Genetics, University of Leipzig Medical Center
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Criteria applied: PVS1,PS4,PM2_SUP,PP4

Aug 01, 2024
3billion
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The variant is observed at an extremely low frequency in the gnomAD v4.0.0 dataset (total allele frequency: <0.001%). Predicted Consequence/Location: Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000220152 /PMID: 9180088 /3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

May 18, 2017
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:clinical testing

not provided Pathogenic:7
Sep 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

NF1: PVS1, PM2, PM6, PS4:Moderate, PP1

Aug 23, 2021
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

PVS1, PP5, PP1, BS2

Jan 24, 2024
Quest Diagnostics Nichols Institute San Juan Capistrano
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The NF1 c.4537C>T (p.Arg1513*) variant causes the premature termination of NF1 protein synthesis. This variant has been reported in the published literature in individuals with neurofibromatosis 1 (NF1) (PMIDs: 34427956 (2022), 31533651 (2019), 26969325 (2016), 17914445 (2008), 17209131 (2007), 14722917 (2004)), leukemia (PMID: 9180088 (1997)), and breast cancer (PMID: 30530636 (2019)). The frequency of this variant in the general population, 0.000008 (2/251346 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic.

Sep 06, 2022
GeneDx
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 10862084, 29957862, 16941471, 21354044, 18041031, 12552569, 17209131, 24676424, 22155606, 24789688, 27838393, 31717729, 31533797, 34427956, 31980526, 17914445, 10607834, 9180088, 25525159, 14517963, 23668869, 24932921, 29506128, 30530636, 10712197, 16479075, 26969325, 15060124, 15146469, 20687928, 31730495, 31533651, 31370276, 29625052, 32005694, 34426522, 34055682, 31776437, 33344560, 31783133)

Laboratoire de Génétique Moléculaire, CHU Bordeaux
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Jul 08, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The NF1 c.4600C>T; p.Arg1534Ter variant (rs760703505), also known as c.4537C>T; p.Arg1513Ter, is reported in the medical literature in several individuals affected with neurofibromatosis type 1 (Fahsold 2000, Hutter 2016, Jeong 2006, Ko 2013, Side 1997, Valero 2011). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 220152), and only observed on two alleles in the Genome Aggregation Database (v.2.1.1), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Fahsold R et al. Minor lesion mutational spectrum of the entire NF1 gene does not explain its high mutability but points to a functional domain upstream of the GAP-related domain. Am J Hum Genet. 2000 Mar;66(3):790-818. PMID: 10712197. Hutter S et al. No correlation between NF1 mutation position and risk of optic pathway glioma in 77 unrelated NF1 patients. Hum Genet. 2016 May;135(5):469-75. PMID: 26969325. Jeong SY et al. The spectrum of NF1 mutations in Korean patients with neurofibromatosis type 1. J Korean Med Sci. 2006 Feb;21(1):107-12. PMID: 16479075. Ko JM et al. Mutation spectrum of NF1 and clinical characteristics in 78 Korean patients with neurofibromatosis type 1. Pediatr Neurol. 2013 Jun;48(6):447-53. PMID: 23668869. Side L et al. Homozygous inactivation of the NF1 gene in bone marrow cells from children with neurofibromatosis type 1 and malignant myeloid disorders. N Engl J Med. 1997 Jun 12;336(24):1713-20. PMID: 9180088. Valero MC et al. A highly sensitive genetic protocol to detect NF1 mutations. J Mol Diagn. 2011 Mar;13(2):113-22. PMID: 21354044.

Dec 14, 2017
Athena Diagnostics
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Hereditary cancer-predisposing syndrome Pathogenic:2
Jan 18, 2016
Ambry Genetics
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The p.R1534* pathogenic mutation (also known as c.4600C>T), located in coding exon 35 of the NF1 gene, results from a C to T substitution at nucleotide position 4600. This changes the amino acid from an arginine to a stop codon within coding exon 35. This mutation has been observed in multiple neurofibromatosis type 1 (NF1) families,<span style="background-color:initial">including one family in which the mutation segregated with NF1 in a proband diagnosed with juvenile myelomonocytic leukemia at 14 months and his affected mother (<span style="background-color:initial">Ko JMet al. Pediatr. Neurol. 2013 Jun;48(6):447-53,Side Let al. N. Engl. J. Med. 1997 Jun;336(24):1713-20; ​DuatRodriguez A et al.AnPediatr(Barc). 2015 Sep;83(3):173-82<span style="background-color:initial">). In addition to the clinical information presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).<span style="background-color:initial">This mutation is also known as p.R1513* (c.4537C>T) in published literature.

Sep 15, 2021
Sema4, Sema4
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:curation

Subcutaneous neurofibroma;C1857790:Thoracic scoliosis;C1861975:Cafe au lait spots, multiple Pathogenic:1
Sep 29, 2014
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Significance:Likely pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Neurofibromatosis, type 1;C4024216:Tibial pseudarthrosis Pathogenic:1
Nov 10, 2018
The Laboratory of Genetics and Metabolism, Hunan Children’s Hospital
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:research

Abnormality of the skin Pathogenic:1
Jul 10, 2021
Kariminejad - Najmabadi Pathology & Genetics Center
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Neurofibromatosis, type 1;C0349639:Juvenile myelomonocytic leukemia;C0553586:Café-au-lait macules with pulmonary stenosis;C1834235:Neurofibromatosis, familial spinal;C2931482:Neurofibromatosis-Noonan syndrome Pathogenic:1
Jun 20, 2024
Fulgent Genetics, Fulgent Genetics
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Gastric cancer Pathogenic:1
Jul 01, 2021
Laboratory for Genotyping Development, RIKEN
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:research

Café-au-lait macules with pulmonary stenosis Pathogenic:1
Oct 04, 2024
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:research

PVS1strong,PS4,PP4

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.54
D
BayesDel_noAF
Pathogenic
0.62
CADD
Pathogenic
37
DANN
Uncertain
1.0
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.93
D
PhyloP100
2.1
Vest4
0.98
GERP RS
5.4
Mutation Taster
=0/200
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs760703505; hg19: chr17-29588751; COSMIC: COSV62191852; API