rs1131691074
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001042492.3(NF1):c.8009C>A(p.Ser2670Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. S2670S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001042492.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.8009C>A | p.Ser2670Ter | stop_gained | 55/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.7946C>A | p.Ser2649Ter | stop_gained | 54/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.8009C>A | p.Ser2670Ter | stop_gained | 55/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 15, 2014 | The p.S2670* pathogenic mutation (also known as c.8009C>A or p.S2649*) located in coding exon 55 of the NF1 gene, results from a C to A substitution at nucleotide position 8009. This changes the amino acid from a serine to a stop codon within coding exon 55. This mutation was reported in a patient with sporadic NF1, whose clinical features included 6 or more cafe-au-lait spots of 0.5cm or greater and pseudarthrosis (<span data-redactor="verified" style="background-color: initial;">Leskelä HV et al. Bone 2009 Feb; 44(2):243-50).<span data-redactor="verified" style="background-color: initial;">In addition to the clinical data 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at