17-31357057-TC-TCC
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001042492.3(NF1):c.7838dup(p.Lys2614GlufsTer20) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
NF1
NM_001042492.3 frameshift
NM_001042492.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.08
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 17-31357057-T-TC is Pathogenic according to our data. Variant chr17-31357057-T-TC is described in ClinVar as [Pathogenic]. Clinvar id is 429012.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.7838dup | p.Lys2614GlufsTer20 | frameshift_variant | 53/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.7775dup | p.Lys2593GlufsTer20 | frameshift_variant | 52/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.7838dup | p.Lys2614GlufsTer20 | frameshift_variant | 53/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neurofibromatosis, type 1 Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Medical Genetics, University of Parma | Feb 02, 2017 | - - |
Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 02, 2016 | The c.7775dupC pathogenic mutation, located in coding exon 52 of the NF1 gene, results from a duplication of C at nucleotide position 7775, causing a translational frameshift with a predicted alternate stop codon (p.K2593Efs*20). This mutation has been reported in one individual with a clinical diagnosis of neurofibromatosis type 1 (Pasmant E et al. Eur. J. Hum. Genet., 2015 May;23:596-601). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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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