chr22-29665030-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000268.4(NF2):āc.851A>Gā(p.Lys284Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K284T) 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.851A>G | p.Lys284Arg | missense_variant | 9/16 | ENST00000338641.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF2 | ENST00000338641.10 | c.851A>G | p.Lys284Arg | missense_variant | 9/16 | 1 | NM_000268.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251186Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135780
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461596Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727102
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Neurofibromatosis, type 2 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 18, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2022 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 566844). This variant has not been reported in the literature in individuals affected with NF2-related conditions. This variant is present in population databases (rs764034925, gnomAD 0.0009%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 284 of the NF2 protein (p.Lys284Arg). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 12, 2023 | The p.K284R variant (also known as c.851A>G), located in coding exon 9 of the NF2 gene, results from an A to G substitution at nucleotide position 851. The lysine at codon 284 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at