rs1489623582
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000548.5(TSC2):c.215A>G(p.Lys72Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K72N) has been classified as Likely benign.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.215A>G | p.Lys72Arg | missense_variant | 3/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.215A>G | p.Lys72Arg | missense_variant | 3/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152144Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250948Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135836
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461620Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727100
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152144Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74356
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 16, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Tuberous sclerosis syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Oct 27, 2023 | This missense variant replaces lysine with arginine at codon 72 of the TSC2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC2-related disorders in the literature. This variant has been identified in 2/250948 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Isolated focal cortical dysplasia type II Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 09, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 29, 2022 | The p.K72R variant (also known as c.215A>G), located in coding exon 2 of the TSC2 gene, results from an A to G substitution at nucleotide position 215. The lysine at codon 72 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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