rs747237113
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PM1PP3_ModerateBS2
The NM_000548.5(TSC2):c.886G>A(p.Val296Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000377 in 1,593,554 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V296L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
Publications
- tuberous sclerosisInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- tuberous sclerosis 2Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Ambry Genetics
- lymphangioleiomyomatosisInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- tuberous sclerosis complexInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00000464 AC: 1AN: 215604 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.00000347 AC: 5AN: 1441318Hom.: 0 Cov.: 32 AF XY: 0.00000280 AC XY: 2AN XY: 714914 show subpopulations
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74382 show subpopulations
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Uncertain:1Benign:1
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Lymphangiomyomatosis Pathogenic:1
This variant was classified as: Likely pathogenic. -
Cortical tubers Pathogenic:1
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not provided Uncertain:1
Observed in a patient with epilepsy, learning disability, facial angiofibromas, and renal cysts; paternally inherited, although no clinical information was provided for the father (Tumiene et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 18466115, 29286531) -
Hereditary cancer-predisposing syndrome Uncertain:1
The p.V296M variant (also known as c.886G>A), located in coding exon 9 of the TSC2 gene, results from a G to A substitution at nucleotide position 886. The valine at codon 296 is replaced by methionine, an amino acid with highly similar properties. This alteration was detected in an individual with a personal history of epilepsy, specific learning disability, facial angiofibromas and renal cysts (Tumien B et al. Clin Genet, 2018 05;93:1057-1062). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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