chr22-29671848-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000268.4(NF2):c.1022G>T(p.Arg341Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R341G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000268.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF2 | NM_000268.4 | c.1022G>T | p.Arg341Leu | missense_variant | 11/16 | ENST00000338641.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF2 | ENST00000338641.10 | c.1022G>T | p.Arg341Leu | missense_variant | 11/16 | 1 | NM_000268.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251430Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135894
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461804Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727202
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Neurofibromatosis, type 2 Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 27, 2022 | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 485993). This variant has not been reported in the literature in individuals affected with NF2-related conditions. This variant is present in population databases (rs754087071, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 341 of the NF2 protein (p.Arg341Leu). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jan 11, 2024 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 03, 2024 | The p.R341L variant (also known as c.1022G>T), located in coding exon 11 of the NF2 gene, results from a G to T substitution at nucleotide position 1022. The arginine at codon 341 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at