16-2075870-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_000548.5(TSC2):āc.2617C>Gā(p.Leu873Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L873P) has been classified as Uncertain significance.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.2617C>G | p.Leu873Val | missense_variant | 23/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.2617C>G | p.Leu873Val | missense_variant | 23/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74372
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2020 | 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 873 of the TSC2 protein (p.Leu873Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at