rs121434260
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_000268.4(NF2):c.288_290delCTT(p.Phe96del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. F96F) has been classified as Likely benign.
Frequency
Consequence
NM_000268.4 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NF2 | NM_000268.4 | c.288_290delCTT | p.Phe96del | disruptive_inframe_deletion | Exon 3 of 16 | ENST00000338641.10 | NP_000259.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Neurofibromatosis, type 2 Pathogenic:2
PM1, PM2, PM4, PP3,PP5, PP4 -
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Hereditary cancer-predisposing syndrome Uncertain:1
The c.288_290delCTT variant (also known as p.F96del) is located in coding exon 3 of the NF2 gene. This variant results from an in-frame CTT deletion at nucleotide positions 288 to 290. This results in the in-frame deletion of a phenylalanine at codon 96. This variant has been reported in individuals with features of NF2-related schwannomatosis (Cordeiro NJ et al. Dev Med Child Neurol, 2006 Jan;48:58-9; Henson JW et al. Neurol Genet, 2020 Aug;6:e446). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this variant remains unclear. -
SMARCB1-related schwannomatosis Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at