chr22-29674882-G-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000268.4(NF2):c.1387G>T(p.Glu463Ter) 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. E463E) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000268.4 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 |
---|---|---|---|---|---|---|---|
NF2 | NM_000268.4 | c.1387G>T | p.Glu463Ter | stop_gained | 13/16 | ENST00000338641.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF2 | ENST00000338641.10 | c.1387G>T | p.Glu463Ter | stop_gained | 13/16 | 1 | NM_000268.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1420904Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 702766
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Neurofibromatosis, type 2 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 30, 2020 | Loss-of-function variants in NF2 are known to be pathogenic (PMID: 9643284, 16983642). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with neurofibromatosis type 2 (PMID: 7913580). ClinVar contains an entry for this variant (Variation ID: 3294). This sequence change creates a premature translational stop signal (p.Glu463*) in the NF2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 1994 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at